Disorders resulting from defective DNA REPAIR processes or the associated cellular responses to DNA DAMAGE.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically.
A form of IODINE deficiency disorders characterized by an enlargement of the THYROID GLAND in a significantly large fraction of a POPULATION GROUP. Endemic goiter is common in mountainous and iodine-deficient areas of the world where the DIET contains insufficient amount of iodine.
Enlargement of the THYROID GLAND that may increase from about 20 grams to hundreds of grams in human adults. Goiter is observed in individuals with normal thyroid function (euthyroidism), thyroid deficiency (HYPOTHYROIDISM), or hormone overproduction (HYPERTHYROIDISM). Goiter may be congenital or acquired, sporadic or endemic (GOITER, ENDEMIC).
Sodium chloride used in foods.
A condition produced by dietary or metabolic deficiency. The term includes all diseases caused by an insufficient supply of essential nutrients, i.e., protein (or amino acids), vitamins, and minerals. It also includes an inadequacy of calories. (From Dorland, 27th ed; Stedman, 25th ed)
An enzyme that catalyzes the hydrolysis of cerebroside 3-sulfate (sulfatide) to yield a cerebroside and inorganic sulfate. A marked deficiency of arylsulfatase A, which is considered the heat-labile component of cerebroside sulfatase, has been demonstrated in all forms of metachromatic leukodystrophy (LEUKODYSTROPHY, METACHROMATIC). EC 3.1.6.8.
A preparation of oil that contains covalently bound IODINE. It is commonly used as a RADIOCONTRAST AGENT and as a suspension medium for CHEMOTHERAPEUTIC AGENTS.
The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).
I'm sorry for any confusion, but "Sikkim" is not a medical term that has a definition in the field of medicine. It is actually a state in northeastern India, located in the Himalayan mountains. If you have any questions about geographical or political terms, I would be happy to try and help with those as well.
A condition in infancy or early childhood due to an in-utero deficiency of THYROID HORMONES that can be caused by genetic or environmental factors, such as thyroid dysgenesis or HYPOTHYROIDISM in infants of mothers treated with THIOURACIL during pregnancy. Endemic cretinism is the result of iodine deficiency. Clinical symptoms include severe MENTAL RETARDATION, impaired skeletal development, short stature, and MYXEDEMA.
A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.
An autosomal recessive disorder due to defects in PEROXISOME biogenesis which involves more than 13 genes encoding peroxin proteins of the peroxisomal membrane and matrix. Zellweger syndrome is typically seen in the neonatal period with features such as dysmorphic skull; MUSCLE HYPOTONIA; SENSORINEURAL HEARING LOSS; visual compromise; SEIZURES; progressive degeneration of the KIDNEYS and the LIVER. Zellweger-like syndrome refers to phenotypes resembling the neonatal Zellweger syndrome but seen in children or adults with apparently intact peroxisome biogenesis.
Sulfatases are a group of enzymes that catalyze the hydrolysis of sulfate ester bonds in various substrates, playing crucial roles in the metabolism and homeostasis of carbohydrates, proteoglycans, neurotransmitters, and steroid hormones within the body.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
I'm sorry for any confusion, but "India" is not a medical term that can be defined in a medical context. It is a geographical location, referring to the Republic of India, a country in South Asia. If you have any questions related to medical topics or definitions, I would be happy to help with those!
An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of HYPOTHERMIA, feeding difficulties, hypotonia, SEIZURES, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including PROTEIN-LYSINE 6-OXIDASE; CERULOPLASMIN; and SUPEROXIDE DISMUTASE. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. (From Menkes, Textbook of Child Neurology, 5th ed, p125)
A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ULTRAVIOLET RAYS as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
A DNA helicase that is a component of TRANSCRIPTION FACTOR TFIIH. It plays an essential role in NUCLEOTIDE EXCISION REPAIR, and mutations in this protein are associated with XERODERMA PIGMENTOSUM.
A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.
Electron-dense cytoplasmic particles bounded by a single membrane, such as PEROXISOMES; GLYOXYSOMES; and glycosomes.
Disorders resulting from defects in migration of neuronal cells during neurogenesis. Developing nerve cells either fail to migrate or they migrate to incorrect positions resulting in formation of heterotopias, lissencephaly, or other malformations and dysfunctions of the nervous system.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
The inhabitants of rural areas or of small towns classified as rural.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.
Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Transport proteins that carry specific substances in the blood or across cell membranes.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Persistent and disabling ANXIETY.
Those disorders that have a disturbance in mood as their predominant feature.
DNA present in neoplastic tissue.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. (1/46)

DNA double-strand breaks (DSBs) occur at random upon genotoxic stresses and represent obligatory intermediates during physiological DNA rearrangement events such as the V(D)J recombination in the immune system. DSBs, which are among the most toxic DNA lesions, are preferentially repaired by the nonhomologous end-joining (NHEJ) pathway in higher eukaryotes. Failure to properly repair DSBs results in genetic instability, developmental delay, and various forms of immunodeficiency. Here we describe five patients with growth retardation, microcephaly, and immunodeficiency characterized by a profound T+B lymphocytopenia. An increased cellular sensitivity to ionizing radiation, a defective V(D)J recombination, and an impaired DNA-end ligation process both in vivo and in vitro are indicative of a general DNA repair defect in these patients. All five patients carry mutations in the Cernunnos gene, which was identified through cDNA functional complementation cloning. Cernunnos/XLF represents a novel DNA repair factor essential for the NHEJ pathway.  (+info)

Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. (2/46)

PURPOSE: Defective DNA mismatch repair is commonly present in sporadic manifestations of gastrointestinal, endometrial, and other cancers. The pathognomonic molecular manifestation of this repair defect is microsatellite instability (MSI). Here, we test the hypothesis that MSI predicts the clinicopathologic features of endometrial carcinoma. PATIENTS AND METHODS: A retrospective cohort of 473 patients treated for endometrial carcinoma at this institution was identified. All cases were reviewed by a gynecologic pathologist, and clinical information was abstracted from medical records. Using consensus criteria, DNA samples from nontumor and tumor tissue pairs were genotyped for MSI. Associations between MSI status and pathologic and clinical variables were assessed. RESULTS: Ninety-three (20%) of 473 tumors were MSI+. In the MSI+ tumor group compared with the MSI- tumor group, the proportion of advanced compared with early-stage tumors was higher (92% v 81%; P = .01), as was the proportion of tumors of endometrioid compared with nonendometrioid histologic subtype (94% v 23%; P = .001), and the proportion of tumors with myometrial invasion compared with those with none (92% v 78%; P = .01). By multivariate analyses, disease-free survival (hazard ratio, 0.3; 95% CI, 0.2 to 0.7) and disease-specific survival (hazard ratio, 0.3; 95% CI, 0.1 to 0.8) were significantly improved in patients with MSI+ tumors. CONCLUSION: In endometrial carcinoma, the presence of MSI was independently associated with a more favorable clinical outcome.  (+info)

Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer. (3/46)

BACKGROUND: Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer. METHODS: Microsatellite instability and promoter methylation were investigated by PCR, denaturing-polyacrylamide gel electrophoresis and digestion with methylation-specific restriction enzymes. RESULTS: Microsatellite instability was observed in 41% of the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the patients, respectively. BAT25 and BAT26 instability were associated with age and histopathology, respectively. Methylation frequency of the hMLH1 gene promoter was significantly higher in patients displaying a high level of microsatellite instability. Instability at the BAT 26 and D2S123 loci were associated with the MSI-high status. CONCLUSIONS: Our results indicate that microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.  (+info)

Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. (4/46)

A-type lamins are components of the nuclear lamina. Mutations in the gene encoding lamin A are associated with a range of highly degenerative diseases termed laminopathies. To evaluate sensitivity to DNA damage, GFP-tagged lamin A cDNAs with disease-causing mutations were expressed in HeLa cells. The inner nuclear membrane protein emerin was mislocalised upon expression of the muscular dystrophy mutants G232E, Q294P or R386K, which aberrantly assembled into nuclear aggregates, or upon expression of mutants causing progeria syndromes in vivo (lamin A del50, R471C, R527C and L530P). The ability of cells expressing these mutants to form DNA repair foci comprising phosphorylated H2AX in response to mild doses of cisplatin or UV irradiation was markedly diminished, unlike the nearly normal response of cells expressing wild-type GFP-lamin A or disease-causing H222P and R482L mutants. Interestingly, mutants that impaired the formation of DNA repair foci mislocalised ATR (for ;ataxia telangiectasia-mutated and Rad3-related') kinase, which is a key sensor in the response to DNA damage. Our results suggest that a subset of lamin A mutants might hinder the response of components of the DNA repair machinery to DNA damage by altering interactions with chromatin.  (+info)

DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. (5/46)

Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. Cancer cells are often defective in one of six major DNA repair pathways, namely: mismatch repair, base excision repair, nucleotide excision repair, homologous recombination, nonhomologous endjoining and translesion synthesis. The specific DNA repair pathway affected is predictive of the kinds of mutations, the tumor drug sensitivity, and the treatment outcome. The study of rare inherited DNA repair disorders, such as Fanconi anemia, has yielded new insights to drug sensitivity and treatment of sporadic cancers, such as breast or ovarian epithelial tumors, in the general population. The Fanconi anemia pathway is an example of how DNA repair pathways can be deregulated in cancer cells and how biomarkers of the integrity of these pathways could be useful as a guide to cancer management and may be used in the development of novel therapeutic agents.  (+info)

Autosomal recessive cerebellar ataxias. (6/46)

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2-4/100,000), ataxia-telangiectasia (1-2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, alpha-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia.  (+info)

Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency. (7/46)

Single-base lesions in DNA are repaired predominantly by base excision repair (BER). DNA polymerase beta (pol beta) is the polymerase of choice in the preferred single-nucleotide BER pathway. The characteristic phenotype of mouse fibroblasts with a deletion of the pol beta gene is moderate hypersensitivity to monofunctional alkylating agents, e.g., methyl methanesulfonate (MMS). Increased sensitivity to MMS is also seen in the absence of pol beta partner proteins XRCC1 and PARP-1, and under conditions where BER efficiency is reduced by synthetic inhibitors. PARP activity plays a major role in protection against MMS-induced cytotoxicity, and cells treated with a combination of non-toxic concentrations of MMS and a PARP inhibitor undergo cell cycle arrest and die by a Chk1-dependent apoptotic pathway. Since BER-deficient cells and tumors are similarly hypersensitive to the clinically used chemotherapeutic methylating agent temozolomide, modulation of DNA damage-induced cell signaling pathways, as well as BER, are attractive targets for potentiating chemotherapy.  (+info)

DNA damage responses in neural cells: Focus on the telomere. (8/46)

Postmitotic neurons must survive for the entire life of the organism and be able to respond adaptively to adverse conditions of oxidative and genotoxic stress. Unrepaired DNA damage can trigger apoptosis of neurons which is typically mediated by the ataxia telangiectasia mutated (ATM)-p53 pathway. As in all mammalian cells, telomeres in neurons consist of TTAGGG DNA repeats and several associated proteins that form a nucleoprotein complex that prevents chromosome ends from being recognized as double strand breaks. Proteins that stabilize telomeres include TRF1 and TRF2, and proteins known to play important roles in DNA damage responses and DNA repair including ATM, Werner and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). We have been performing studies of developing and adult neurons aimed at understanding the effects of global and telomere-directed DNA damage responses in neuronal plasticity and survival in the contexts of aging and neurodegenerative disorders. Deficits in specific DNA repair proteins, including DNA-PKcs and uracil DNA glycosylase (UDG), render neurons vulnerable to adverse conditions of relevance to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and stroke. Similarly, early postmitotic neurons with reduced telomerase activity exhibit accentuated responses to DNA damage and are prone to apoptosis demonstrating a pivotal role for telomere maintenance in both mitotic cells and postmitotic neurons. Our recent findings suggest key roles for TRF2 in regulating the differentiation and survival of neurons. TRF2 affects cell survival and differentiation by modulating DNA damage pathways, and gene expression. A better understanding of the molecular mechanisms by which neurons respond to global and telomere-specific DNA damage may reveal novel strategies for prevention and treatment of neurodegenerative disorders. Indeed, work in this and other laboratories has shown that dietary folic acid can protect neurons against Alzheimer's disease by keeping homocysteine levels low and thereby minimizing the misincorporation of uracil into DNA in neurons.  (+info)

DNA repair-deficiency disorders are a group of genetic conditions that result from mutations in genes responsible for the repair and maintenance of DNA. These disorders are characterized by increased sensitivity to environmental factors that can damage DNA, such as ultraviolet (UV) radiation, chemicals, and free radicals. As a result, individuals with these disorders have an increased risk of developing various types of cancer, neurological disorders, premature aging, and other health problems.

Examples of DNA repair-deficiency disorders include xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy, and Bloom syndrome. These conditions are typically inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Treatment for DNA repair-deficiency disorders is focused on managing symptoms and preventing complications. This may include avoiding exposure to UV radiation, using sunscreens and protective clothing, and undergoing regular cancer screenings. In some cases, medications or other therapies may be used to treat specific symptoms or complications of the disorder.

DNA repair is the process by which cells identify and correct damage to the DNA molecules that encode their genome. DNA can be damaged by a variety of internal and external factors, such as radiation, chemicals, and metabolic byproducts. If left unrepaired, this damage can lead to mutations, which may in turn lead to cancer and other diseases.

There are several different mechanisms for repairing DNA damage, including:

1. Base excision repair (BER): This process repairs damage to a single base in the DNA molecule. An enzyme called a glycosylase removes the damaged base, leaving a gap that is then filled in by other enzymes.
2. Nucleotide excision repair (NER): This process repairs more severe damage, such as bulky adducts or crosslinks between the two strands of the DNA molecule. An enzyme cuts out a section of the damaged DNA, and the gap is then filled in by other enzymes.
3. Mismatch repair (MMR): This process repairs errors that occur during DNA replication, such as mismatched bases or small insertions or deletions. Specialized enzymes recognize the error and remove a section of the newly synthesized strand, which is then replaced by new nucleotides.
4. Double-strand break repair (DSBR): This process repairs breaks in both strands of the DNA molecule. There are two main pathways for DSBR: non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly rejoins the broken ends, while HR uses a template from a sister chromatid to repair the break.

Overall, DNA repair is a crucial process that helps maintain genome stability and prevent the development of diseases caused by genetic mutations.

Iodine is an essential trace element that is necessary for the production of thyroid hormones in the body. These hormones play crucial roles in various bodily functions, including growth and development, metabolism, and brain development during pregnancy and infancy. Iodine can be found in various foods such as seaweed, dairy products, and iodized salt. In a medical context, iodine is also used as an antiseptic to disinfect surfaces, wounds, and skin infections due to its ability to kill bacteria, viruses, and fungi.

Endemic goiter refers to a condition of abnormal enlargement of the thyroid gland that is prevalent in a particular geographic area due to deficiency of iodine in the diet or drinking water. The lack of iodine leads to decreased production of thyroid hormones, which in turn stimulates the thyroid gland to grow and attempt to increase hormone production. This results in the visible enlargement of the thyroid gland, known as a goiter. Endemic goiter is preventable through iodine supplementation in the diet or through iodized salt.

Goiter is a medical term that refers to an enlarged thyroid gland. The thyroid gland is a small, butterfly-shaped gland located in the front of your neck below the larynx or voice box. It produces hormones that regulate your body's metabolism, growth, and development.

Goiter can vary in size and may be visible as a swelling at the base of the neck. It can be caused by several factors, including iodine deficiency, autoimmune disorders, thyroid cancer, pregnancy, or the use of certain medications. Depending on the underlying cause and the severity of the goiter, treatment options may include medication, surgery, or radioactive iodine therapy.

Sodium chloride, commonly known as salt, is an essential electrolyte in dietary intake. It is a chemical compound made up of sodium (Na+) and chloride (Cl-) ions. In a medical context, particularly in nutrition and dietetics, "sodium chloride, dietary" refers to the consumption of this compound in food sources.

Sodium plays a crucial role in various bodily functions such as maintaining fluid balance, assisting nerve impulse transmission, and contributing to muscle contraction. The Dietary Guidelines for Americans recommend limiting sodium intake to less than 2,300 milligrams (mg) per day and further suggest an ideal limit of no more than 1,500 mg per day for most adults, especially those with high blood pressure. However, the average American consumes more than twice the recommended amount, primarily from processed and prepared foods. Excessive sodium intake can lead to high blood pressure and increase the risk of heart disease and stroke.

Deficiency diseases are a group of medical conditions that occur when an individual's diet lacks essential nutrients, such as vitamins and minerals. These diseases develop because the body needs these nutrients to function correctly, and without them, various bodily functions can become impaired, leading to disease.

Deficiency diseases can manifest in many different ways, depending on which nutrient is lacking. For example:

* Vitamin A deficiency can lead to night blindness and increased susceptibility to infectious diseases.
* Vitamin C deficiency can result in scurvy, a condition characterized by fatigue, swollen gums, joint pain, and anemia.
* Vitamin D deficiency can cause rickets in children, a disease that leads to weakened bones and skeletal deformities.
* Iron deficiency can result in anemia, a condition in which the blood lacks adequate healthy red blood cells.

Preventing deficiency diseases involves eating a balanced diet that includes a variety of foods from all the major food groups. In some cases, supplements may be necessary to ensure adequate nutrient intake, especially for individuals who have restricted diets or medical conditions that affect nutrient absorption.

Cerebroside-sulfatase is an enzyme that plays a crucial role in the breakdown and recycling of lipids within the body, particularly in the brain. Its primary function is to break down a type of lipid called cerebroside sulfate, which is a major component of the myelin sheath that surrounds and insulates nerve fibers in the brain and nervous system.

Cerebroside-sulfatase deficiency can lead to a group of genetic disorders known as the mucopolysaccharidoses (MPS), specifically MPS IIIB or Sanfilippo syndrome B. In this condition, the lack of cerebroside-sulfatase activity leads to an accumulation of cerebroside sulfate in the lysosomes of cells, resulting in progressive neurological deterioration and developmental delays.

Iodized oil is a type of oil, often sesame or soybean oil, that has been artificially enriched with the essential micromineral iodine. It is typically used as a medical treatment for iodine deficiency disorders, such as goiter and cretinism, and for preventing their occurrence.

The iodization process involves binding iodine to the oil molecules, which allows the iodine to be slowly released and absorbed by the body over an extended period of time. This makes it an effective long-term supplement for maintaining adequate iodine levels in the body. Iodized oil is usually administered via intramuscular injection, and its effects can last for several months to a year.

It's important to note that while iodized oil is a valuable tool in addressing iodine deficiency on an individual level, global public health initiatives have focused on adding iodine to table salt (known as iodization of salt) as a more widespread and sustainable solution for eliminating iodine deficiency disorders.

A base pair mismatch is a type of mutation that occurs during the replication or repair of DNA, where two incompatible nucleotides pair up instead of the usual complementary bases (adenine-thymine or cytosine-guanine). This can result in the substitution of one base pair for another and may lead to changes in the genetic code, potentially causing errors in protein synthesis and possibly contributing to genetic disorders or diseases, including cancer.

I'm sorry for any confusion, but "Sikkim" is not a medical term. It is actually the name of a state in India, located in the northeastern part of the country. If you have any questions about medical terminology or concepts, I'd be happy to try and help answer those for you!

Congenital hypothyroidism is a medical condition characterized by the partial or complete absence of thyroid hormone production in the baby's body at birth. The thyroid gland, which is located in the front of the neck, produces hormones that are essential for normal growth and development of the brain and body.

Congenital hypothyroidism can occur due to various reasons such as the absence or abnormal development of the thyroid gland, or a defect in the production or regulation of thyroid hormones. In some cases, it may be caused by genetic mutations that affect the development or function of the thyroid gland.

If left untreated, congenital hypothyroidism can lead to mental and physical retardation, growth problems, and other health issues. Therefore, it is important to diagnose and treat this condition as early as possible, usually within the first few weeks of life. Treatment typically involves replacing the missing thyroid hormones with synthetic medications, which are safe and effective when administered under a doctor's supervision.

DNA mismatch repair (MMR) is a cellular process that helps to correct errors that occur during DNA replication and recombination. This mechanism plays a critical role in maintaining the stability of the genome by reducing the rate of mutations.

The MMR system recognizes and repairs base-base mismatches and small insertions or deletions (indels) that can arise due to slippage of DNA polymerase during replication. The process involves several proteins, including MutSα or MutSβ, which recognize the mismatch, and MutLα, which acts as a endonuclease to cleave the DNA near the mismatch. Excision of the mismatched region is then carried out by exonucleases, followed by resynthesis of the repaired strand using the correct template.

Defects in MMR genes have been linked to various human diseases, including hereditary nonpolyposis colorectal cancer (HNPCC) and other types of cancer. In HNPCC, mutations in MMR genes lead to an accumulation of mutations in critical genes, which can ultimately result in the development of cancer.

DNA repair enzymes are a group of enzymes that are responsible for identifying and correcting damage to the DNA molecule. These enzymes play a critical role in maintaining the integrity of an organism's genetic material, as they help to ensure that the information stored in DNA is accurately transmitted during cell division and reproduction.

There are several different types of DNA repair enzymes, each responsible for correcting specific types of damage. For example, base excision repair enzymes remove and replace damaged or incorrect bases, while nucleotide excision repair enzymes remove larger sections of damaged DNA and replace them with new nucleotides. Other types of DNA repair enzymes include mismatch repair enzymes, which correct errors that occur during DNA replication, and double-strand break repair enzymes, which are responsible for fixing breaks in both strands of the DNA molecule.

Defects in DNA repair enzymes have been linked to a variety of diseases, including cancer, neurological disorders, and premature aging. For example, individuals with xeroderma pigmentosum, a rare genetic disorder characterized by an increased risk of skin cancer, have mutations in genes that encode nucleotide excision repair enzymes. Similarly, defects in mismatch repair enzymes have been linked to hereditary nonpolyposis colorectal cancer, a type of colon cancer that is inherited and tends to occur at a younger age than sporadic colon cancer.

Overall, DNA repair enzymes play a critical role in maintaining the stability and integrity of an organism's genetic material, and defects in these enzymes can have serious consequences for human health.

MutS Homolog 2 (MSH2) Protein is a type of protein involved in the DNA repair process in cells. It is a member of the MutS family of proteins, which are responsible for identifying and correcting mistakes that occur during DNA replication. MSH2 forms a complex with another MutS homolog, MSH6, and this complex plays a crucial role in recognizing and binding to mismatched base pairs in the DNA. Once bound, the complex recruits other proteins to repair the damage and restore the integrity of the DNA. Defects in the MSH2 gene have been linked to an increased risk of certain types of cancer, including hereditary non-polyposis colorectal cancer (HNPCC) and uterine cancer.

Zellweger Syndrome is a rare genetic disorder that affects the development and function of multiple organ systems in the body. It is part of a group of conditions known as peroxisome biogenesis disorders (PBDs), which are characterized by abnormalities in the structure and function of peroxisomes, which are cellular structures that break down fatty acids and other substances in the body.

Zellweger Syndrome is caused by mutations in one or more genes involved in the formation and maintenance of peroxisomes. As a result, people with this condition have reduced levels of certain enzymes that are necessary for normal brain development, as well as for the breakdown of fats and other substances in the body.

Symptoms of Zellweger Syndrome typically appear within the first few months of life and may include:

* Severe developmental delays and intellectual disability
* Hypotonia (low muscle tone) and poor motor skills
* Vision and hearing problems
* Facial abnormalities, such as a high forehead, wide-set eyes, and a prominent nasal bridge
* Liver dysfunction and jaundice
* Seizures
* Feeding difficulties and failure to thrive

There is no cure for Zellweger Syndrome, and treatment is focused on managing the symptoms of the condition. The prognosis for people with this disorder is generally poor, with most individuals not surviving beyond the first year of life. However, some individuals with milder forms of the condition may live into early childhood or adolescence.

Sulfatases are a group of enzymes that play a crucial role in the metabolism of sulfated steroids, glycosaminoglycans (GAGs), and other sulfated molecules. These enzymes catalyze the hydrolysis of sulfate groups from these substrates, converting them into their respective unsulfated forms.

The human genome encodes for several different sulfatases, each with specificity towards particular types of sulfated substrates. For instance, some sulfatases are responsible for removing sulfate groups from steroid hormones and neurotransmitters, while others target GAGs like heparan sulfate, dermatan sulfate, and keratan sulfate.

Defects in sulfatase enzymes can lead to various genetic disorders, such as multiple sulfatase deficiency (MSD), X-linked ichthyosis, and mucopolysaccharidosis (MPS) type IIIC (Sanfilippo syndrome type C). These conditions are characterized by the accumulation of sulfated molecules in different tissues, resulting in progressive damage to multiple organs and systems.

Immunologic deficiency syndromes refer to a group of disorders characterized by defective functioning of the immune system, leading to increased susceptibility to infections and malignancies. These deficiencies can be primary (genetic or congenital) or secondary (acquired due to environmental factors, medications, or diseases).

Primary immunodeficiency syndromes (PIDS) are caused by inherited genetic mutations that affect the development and function of immune cells, such as T cells, B cells, and phagocytes. Examples include severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, and X-linked agammaglobulinemia.

Secondary immunodeficiency syndromes can result from various factors, including:

1. HIV/AIDS: Human Immunodeficiency Virus infection leads to the depletion of CD4+ T cells, causing profound immune dysfunction and increased vulnerability to opportunistic infections and malignancies.
2. Medications: Certain medications, such as chemotherapy, immunosuppressive drugs, and long-term corticosteroid use, can impair immune function and increase infection risk.
3. Malnutrition: Deficiencies in essential nutrients like protein, vitamins, and minerals can weaken the immune system and make individuals more susceptible to infections.
4. Aging: The immune system naturally declines with age, leading to an increased incidence of infections and poorer vaccine responses in older adults.
5. Other medical conditions: Chronic diseases such as diabetes, cancer, and chronic kidney or liver disease can also compromise the immune system and contribute to immunodeficiency syndromes.

Immunologic deficiency syndromes require appropriate diagnosis and management strategies, which may include antimicrobial therapy, immunoglobulin replacement, hematopoietic stem cell transplantation, or targeted treatments for the underlying cause.

DNA damage refers to any alteration in the structure or composition of deoxyribonucleic acid (DNA), which is the genetic material present in cells. DNA damage can result from various internal and external factors, including environmental exposures such as ultraviolet radiation, tobacco smoke, and certain chemicals, as well as normal cellular processes such as replication and oxidative metabolism.

Examples of DNA damage include base modifications, base deletions or insertions, single-strand breaks, double-strand breaks, and crosslinks between the two strands of the DNA helix. These types of damage can lead to mutations, genomic instability, and chromosomal aberrations, which can contribute to the development of diseases such as cancer, neurodegenerative disorders, and aging-related conditions.

The body has several mechanisms for repairing DNA damage, including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. However, if the damage is too extensive or the repair mechanisms are impaired, the cell may undergo apoptosis (programmed cell death) to prevent the propagation of potentially harmful mutations.

I'm sorry for any confusion, but "India" is not a medical term or concept. It is a country in South Asia, the second-most populous country in the world, known for its rich history, diverse culture, and numerous contributions to various fields including medicine. If you have any questions related to medical topics, I would be happy to help answer them!

Menkes kinky hair syndrome, also known as Menkes disease or Steely hair syndrome, is a rare X-linked recessive genetic disorder caused by mutations in the ATP7A gene. This gene provides instructions for making a protein that plays an essential role in the body's ability to absorb and utilize copper, which is necessary for various enzymes involved in vital functions such as energy production, antioxidant activity, connective tissue synthesis, and neurotransmitter synthesis.

The main features of Menkes kinky hair syndrome include:

1. Kinky or steely hypopigmented hair: The hair is often sparse, brittle, and has a characteristic steel wool appearance due to abnormal keratin formation caused by copper deficiency.
2. Neurological symptoms: These may include developmental delays, seizures, hypotonia (low muscle tone), and progressive neurodegeneration leading to severe intellectual disability.
3. Connective tissue abnormalities: Loose skin, joint laxity, hernias, and fragile blood vessels are common features of the condition.
4. Growth failure: Affected individuals often have poor growth and weight gain.
5. Other symptoms: Menkes kinky hair syndrome can also cause gastrointestinal problems, cardiovascular issues, and temperature regulation difficulties.

The onset of symptoms typically occurs within the first few months of life, with most affected children not surviving beyond early childhood due to the severity of their neurological impairments. However, some milder forms of the disorder have been reported, which may allow for a longer lifespan and less severe symptoms.

Xeroderma Pigmentosum (XP) is a rare, genetic disorder that affects the body's ability to repair damage to DNA caused by ultraviolet (UV) radiation from sunlight. The condition results in extreme sensitivity to UV light. People with XP develop freckles and moles on sun-exposed skin at an early age, and are prone to developing various forms of skin cancer. In severe cases, the disease may also affect the eyes and nervous system.

The disorder is caused by mutations in genes that are responsible for repairing damaged DNA. If not diagnosed and managed properly, XP can lead to serious health complications, including disability and death. Treatment typically involves strict sun protection measures, such as avoiding sunlight, using sunscreen, wearing protective clothing, and in some cases, medication or surgery.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

The thyroid gland is a major endocrine gland located in the neck, anterior to the trachea and extends from the lower third of the Adams apple to the suprasternal notch. It has two lateral lobes, connected by an isthmus, and sometimes a pyramidal lobe. This gland plays a crucial role in the metabolism, growth, and development of the human body through the production of thyroid hormones (triiodothyronine/T3 and thyroxine/T4) and calcitonin. The thyroid hormones regulate body temperature, heart rate, and the production of protein, while calcitonin helps in controlling calcium levels in the blood. The function of the thyroid gland is controlled by the hypothalamus and pituitary gland through the thyroid-stimulating hormone (TSH).

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

According to the medical definition, ultraviolet (UV) rays are invisible radiations that fall in the range of the electromagnetic spectrum between 100-400 nanometers. UV rays are further divided into three categories: UVA (320-400 nm), UVB (280-320 nm), and UVC (100-280 nm).

UV rays have various sources, including the sun and artificial sources like tanning beds. Prolonged exposure to UV rays can cause damage to the skin, leading to premature aging, eye damage, and an increased risk of skin cancer. UVA rays penetrate deeper into the skin and are associated with skin aging, while UVB rays primarily affect the outer layer of the skin and are linked to sunburns and skin cancer. UVC rays are the most harmful but fortunately, they are absorbed by the Earth's atmosphere and do not reach the surface.

Healthcare professionals recommend limiting exposure to UV rays, wearing protective clothing, using broad-spectrum sunscreen with an SPF of at least 30, and avoiding tanning beds to reduce the risk of UV-related health problems.

Microsatellite repeats, also known as short tandem repeats (STRs), are repetitive DNA sequences made up of units of 1-6 base pairs that are repeated in a head-to-tail manner. These repeats are spread throughout the human genome and are highly polymorphic, meaning they can have different numbers of repeat units in different individuals.

Microsatellites are useful as genetic markers because of their high degree of variability. They are commonly used in forensic science to identify individuals, in genealogy to trace ancestry, and in medical research to study genetic diseases and disorders. Mutations in microsatellite repeats have been associated with various neurological conditions, including Huntington's disease and fragile X syndrome.

Microsatellite instability (MSI) is a genetic phenomenon characterized by alterations in the number of repeat units in microsatellites, which are short repetitive DNA sequences distributed throughout the genome. MSI arises due to defects in the DNA mismatch repair system, leading to accumulation of errors during DNA replication and cell division.

This condition is often associated with certain types of cancer, such as colorectal, endometrial, and gastric cancers. The presence of MSI in tumors may indicate a better prognosis and potential response to immunotherapy, particularly those targeting PD-1 or PD-L1 pathways.

MSI is typically determined through molecular testing, which compares the length of microsatellites in normal and tumor DNA samples. A high level of instability, known as MSI-High (MSI-H), is indicative of a dysfunctional mismatch repair system and increased likelihood of cancer development.

Xeroderma Pigmentosum Group D Protein, also known as XPD protein, is a component of the nucleotide excision repair complex (NER) in humans. The NER complex is responsible for repairing damaged DNA, including DNA that has been damaged by ultraviolet (UV) light.

The XPD protein is an ATP-dependent helicase that unwinds double-stranded DNA during the NER process. Mutations in the gene that encodes the XPD protein can lead to a genetic disorder called xeroderma pigmentosum (XP), which is characterized by increased sensitivity to UV light and a high risk of skin cancer.

There are several subtypes of XP, and mutations in the XPD gene can cause XP group D. This form of XP is also associated with progressive neurodegeneration and cognitive impairment. The exact mechanism by which XPD mutations lead to these neurological symptoms is not fully understood, but it is thought to be related to defects in transcription-coupled repair (TCR), a subpathway of NER that preferentially repairs DNA damage in the transcribed strand of active genes.

Thyrotropin, also known as thyroid-stimulating hormone (TSH), is a hormone secreted by the anterior pituitary gland. Its primary function is to regulate the production and release of thyroxine (T4) and triiodothyronine (T3) hormones from the thyroid gland. Thyrotropin binds to receptors on the surface of thyroid follicular cells, stimulating the uptake of iodide and the synthesis and release of T4 and T3. The secretion of thyrotropin is controlled by the hypothalamic-pituitary-thyroid axis: thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the release of thyrotropin, while T3 and T4 inhibit its release through a negative feedback mechanism.

Microbodies are small, membrane-bound organelles found in the cells of eukaryotic organisms. They typically measure between 0.2 to 0.5 micrometers in diameter and play a crucial role in various metabolic processes, particularly in the detoxification of harmful substances and the synthesis of lipids.

There are several types of microbodies, including:

1. Peroxisomes: These are the most common type of microbody. They contain enzymes that help break down fatty acids and amino acids, producing hydrogen peroxide as a byproduct. Another set of enzymes within peroxisomes then converts the harmful hydrogen peroxide into water and oxygen, thus detoxifying the cell.
2. Glyoxysomes: These microbodies are primarily found in plants and some fungi. They contain enzymes involved in the glyoxylate cycle, a metabolic pathway that helps convert stored fats into carbohydrates during germination.
3. Microbody-like particles (MLPs): These are smaller organelles found in certain protists and algae. Their functions are not well understood but are believed to be involved in lipid metabolism.

It is important to note that microbodies do not have a uniform structure or function across all eukaryotic cells, and their specific roles can vary depending on the organism and cell type.

Neuronal migration disorders (NMDs) are a group of genetic conditions that affect the development and migration of neurons (nerve cells) in the brain during embryonic development. These disorders result from abnormalities in the genetic code that control the movement and organization of neurons as they migrate to their proper positions in the brain.

NMDs can cause a wide range of neurological symptoms, depending on which areas of the brain are affected and the severity of the disorder. Symptoms may include intellectual disability, developmental delay, seizures, motor abnormalities, vision or hearing problems, and behavioral issues. Some NMDs may also be associated with structural brain abnormalities that can be seen on imaging studies.

Examples of neuronal migration disorders include lissencephaly, pachygyria, heterotopias, and agyria. These conditions are typically diagnosed through a combination of clinical evaluation, genetic testing, and neuroimaging studies. Treatment for NMDs is generally supportive and may involve medications, therapies, and surgical interventions to manage symptoms and improve quality of life.

Adaptor proteins are a type of protein that play a crucial role in intracellular signaling pathways by serving as a link between different components of the signaling complex. Specifically, "signal transducing adaptor proteins" refer to those adaptor proteins that are involved in signal transduction processes, where they help to transmit signals from the cell surface receptors to various intracellular effectors. These proteins typically contain modular domains that allow them to interact with multiple partners, thereby facilitating the formation of large signaling complexes and enabling the integration of signals from different pathways.

Signal transducing adaptor proteins can be classified into several families based on their structural features, including the Src homology 2 (SH2) domain, the Src homology 3 (SH3) domain, and the phosphotyrosine-binding (PTB) domain. These domains enable the adaptor proteins to recognize and bind to specific motifs on other signaling molecules, such as receptor tyrosine kinases, G protein-coupled receptors, and cytokine receptors.

One well-known example of a signal transducing adaptor protein is the growth factor receptor-bound protein 2 (Grb2), which contains an SH2 domain that binds to phosphotyrosine residues on activated receptor tyrosine kinases. Grb2 also contains an SH3 domain that interacts with proline-rich motifs on other signaling proteins, such as the guanine nucleotide exchange factor SOS. This interaction facilitates the activation of the Ras small GTPase and downstream signaling pathways involved in cell growth, differentiation, and survival.

Overall, signal transducing adaptor proteins play a critical role in regulating various cellular processes by modulating intracellular signaling pathways in response to extracellular stimuli. Dysregulation of these proteins has been implicated in various diseases, including cancer and inflammatory disorders.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

Prevalence, in medical terms, refers to the total number of people in a given population who have a particular disease or condition at a specific point in time, or over a specified period. It is typically expressed as a percentage or a ratio of the number of cases to the size of the population. Prevalence differs from incidence, which measures the number of new cases that develop during a certain period.

Hereditary Nonpolyposis Colorectal Neoplasms (HNPCC), also known as Lynch Syndrome, is a genetic disorder that significantly increases the risk of developing colorectal cancer and other types of cancer. It is characterized by the mutation in genes responsible for repairing mistakes in the DNA replication process, specifically the mismatch repair genes (MMR).

HNPCC is typically inherited in an autosomal dominant manner, meaning that a person has a 50% chance of inheriting the mutated gene from an affected parent. The syndrome is associated with the development of colorectal cancer at a younger age, usually before 50 years old, and often in the proximal colon. Individuals with HNPCC also have an increased risk for other cancers, including endometrial, stomach, small intestine, ovary, kidney, brain, and skin (sebaceous gland tumors).

Regular surveillance and screening are crucial for early detection and management of colorectal neoplasms in individuals with HNPCC. This typically includes colonoscopies starting at a younger age and performed more frequently than in the general population. Genetic counseling and testing may also be recommended for family members who may have inherited the mutated gene.

A rural population refers to people who live in areas that are outside of urban areas, typically defined as having fewer than 2,000 residents and lacking certain infrastructure and services such as running water, sewage systems, and paved roads. Rural populations often have less access to healthcare services, education, and economic opportunities compared to their urban counterparts. This population group can face unique health challenges, including higher rates of poverty, limited access to specialized medical care, and a greater exposure to environmental hazards such as agricultural chemicals and industrial pollutants.

DNA helicases are a group of enzymes that are responsible for separating the two strands of DNA during processes such as replication and transcription. They do this by unwinding the double helix structure of DNA, using energy from ATP to break the hydrogen bonds between the base pairs. This allows other proteins to access the individual strands of DNA and carry out functions such as copying the genetic code or transcribing it into RNA.

During replication, DNA helicases help to create a replication fork, where the two strands of DNA are separated and new complementary strands are synthesized. In transcription, DNA helicases help to unwind the DNA double helix at the promoter region, allowing the RNA polymerase enzyme to bind and begin transcribing the DNA into RNA.

DNA helicases play a crucial role in maintaining the integrity of the genetic code and are essential for the normal functioning of cells. Defects in DNA helicases have been linked to various diseases, including cancer and neurological disorders.

A frameshift mutation is a type of genetic mutation that occurs when the addition or deletion of nucleotides in a DNA sequence is not divisible by three. Since DNA is read in groups of three nucleotides (codons), which each specify an amino acid, this can shift the "reading frame," leading to the insertion or deletion of one or more amino acids in the resulting protein. This can cause a protein to be significantly different from the normal protein, often resulting in a nonfunctional protein and potentially causing disease. Frameshift mutations are typically caused by insertions or deletions of nucleotides, but they can also result from more complex genetic rearrangements.

Bipolar disorder, also known as manic-depressive illness, is a mental health condition that causes extreme mood swings that include emotional highs (mania or hypomania) and lows (depression). When you become depressed, you may feel sad or hopeless and lose interest or pleasure in most activities. When your mood shifts to mania or hypomania (a less severe form of mania), you may feel euphoric, full of energy, or unusually irritable. These mood swings can significantly affect your job, school, relationships, and overall quality of life.

Bipolar disorder is typically characterized by the presence of one or more manic or hypomanic episodes, often accompanied by depressive episodes. The episodes may be separated by periods of normal mood, but in some cases, a person may experience rapid cycling between mania and depression.

There are several types of bipolar disorder, including:

* Bipolar I Disorder: This type is characterized by the occurrence of at least one manic episode, which may be preceded or followed by hypomanic or major depressive episodes.
* Bipolar II Disorder: This type involves the presence of at least one major depressive episode and at least one hypomanic episode, but no manic episodes.
* Cyclothymic Disorder: This type is characterized by numerous periods of hypomania and depression that are not severe enough to meet the criteria for a full manic or depressive episode.
* Other Specified and Unspecified Bipolar and Related Disorders: These categories include bipolar disorders that do not fit the criteria for any of the other types.

The exact cause of bipolar disorder is unknown, but it appears to be related to a combination of genetic, environmental, and neurochemical factors. Treatment typically involves a combination of medication, psychotherapy, and lifestyle changes to help manage symptoms and prevent relapses.

A cross-sectional study is a type of observational research design that examines the relationship between variables at one point in time. It provides a snapshot or a "cross-section" of the population at a particular moment, allowing researchers to estimate the prevalence of a disease or condition and identify potential risk factors or associations.

In a cross-sectional study, data is collected from a sample of participants at a single time point, and the variables of interest are measured simultaneously. This design can be used to investigate the association between exposure and outcome, but it cannot establish causality because it does not follow changes over time.

Cross-sectional studies can be conducted using various data collection methods, such as surveys, interviews, or medical examinations. They are often used in epidemiology to estimate the prevalence of a disease or condition in a population and to identify potential risk factors that may contribute to its development. However, because cross-sectional studies only provide a snapshot of the population at one point in time, they cannot account for changes over time or determine whether exposure preceded the outcome.

Therefore, while cross-sectional studies can be useful for generating hypotheses and identifying potential associations between variables, further research using other study designs, such as cohort or case-control studies, is necessary to establish causality and confirm any findings.

Antineoplastic agents, alkylating, are a class of chemotherapeutic drugs that work by alkylating (adding alkyl groups) to DNA, which can lead to the death or dysfunction of cancer cells. These agents can form cross-links between strands of DNA, preventing DNA replication and transcription, ultimately leading to cell cycle arrest and apoptosis (programmed cell death). Examples of alkylating agents include cyclophosphamide, melphalan, and cisplatin. While these drugs are designed to target rapidly dividing cancer cells, they can also affect normal cells that divide quickly, such as those in the bone marrow and digestive tract, leading to side effects like anemia, neutropenia, thrombocytopenia, and nausea/vomiting.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

A mental disorder is a syndrome characterized by clinically significant disturbance in an individual's cognition, emotion regulation, or behavior. It's associated with distress and/or impaired functioning in social, occupational, or other important areas of life, often leading to a decrease in quality of life. These disorders are typically persistent and can be severe and disabling. They may be related to factors such as genetics, early childhood experiences, or trauma. Examples include depression, anxiety disorders, bipolar disorder, schizophrenia, and personality disorders. It's important to note that a diagnosis should be made by a qualified mental health professional.

A neoplasm is a tumor or growth that is formed by an abnormal and excessive proliferation of cells, which can be benign or malignant. Neoplasm proteins are therefore any proteins that are expressed or produced in these neoplastic cells. These proteins can play various roles in the development, progression, and maintenance of neoplasms.

Some neoplasm proteins may contribute to the uncontrolled cell growth and division seen in cancer, such as oncogenic proteins that promote cell cycle progression or inhibit apoptosis (programmed cell death). Others may help the neoplastic cells evade the immune system, allowing them to proliferate undetected. Still others may be involved in angiogenesis, the formation of new blood vessels that supply the tumor with nutrients and oxygen.

Neoplasm proteins can also serve as biomarkers for cancer diagnosis, prognosis, or treatment response. For example, the presence or level of certain neoplasm proteins in biological samples such as blood or tissue may indicate the presence of a specific type of cancer, help predict the likelihood of cancer recurrence, or suggest whether a particular therapy will be effective.

Overall, understanding the roles and behaviors of neoplasm proteins can provide valuable insights into the biology of cancer and inform the development of new diagnostic and therapeutic strategies.

Anxiety disorders are a category of mental health disorders characterized by feelings of excessive and persistent worry, fear, or anxiety that interfere with daily activities. They include several different types of disorders, such as:

1. Generalized Anxiety Disorder (GAD): This is characterized by chronic and exaggerated worry and tension, even when there is little or nothing to provoke it.
2. Panic Disorder: This is characterized by recurring unexpected panic attacks and fear of experiencing more panic attacks.
3. Social Anxiety Disorder (SAD): Also known as social phobia, this is characterized by excessive fear, anxiety, or avoidance of social situations due to feelings of embarrassment, self-consciousness, and concern about being judged or viewed negatively by others.
4. Phobias: These are intense, irrational fears of certain objects, places, or situations. When a person with a phobia encounters the object or situation they fear, they may experience panic attacks or other severe anxiety responses.
5. Agoraphobia: This is a fear of being in places where it may be difficult to escape or get help if one has a panic attack or other embarrassing or incapacitating symptoms.
6. Separation Anxiety Disorder (SAD): This is characterized by excessive anxiety about separation from home or from people to whom the individual has a strong emotional attachment (such as a parent, sibling, or partner).
7. Selective Mutism: This is a disorder where a child becomes mute in certain situations, such as at school, but can speak normally at home or with close family members.

These disorders are treatable with a combination of medication and psychotherapy (cognitive-behavioral therapy, exposure therapy). It's important to seek professional help if you suspect that you or someone you know may have an anxiety disorder.

Mood disorders are a category of mental health disorders characterized by significant and persistent changes in mood, affect, and emotional state. These disorders can cause disturbances in normal functioning and significantly impair an individual's ability to carry out their daily activities. The two primary types of mood disorders are depressive disorders (such as major depressive disorder or persistent depressive disorder) and bipolar disorders (which include bipolar I disorder, bipolar II disorder, and cyclothymic disorder).

Depressive disorders involve prolonged periods of low mood, sadness, hopelessness, and a lack of interest in activities. Individuals with these disorders may also experience changes in sleep patterns, appetite, energy levels, concentration, and self-esteem. In severe cases, they might have thoughts of death or suicide.

Bipolar disorders involve alternating episodes of mania (or hypomania) and depression. During a manic episode, individuals may feel extremely elated, energetic, or irritable, with racing thoughts, rapid speech, and impulsive behavior. They might engage in risky activities, have decreased sleep needs, and display poor judgment. In contrast, depressive episodes involve the same symptoms as depressive disorders.

Mood disorders can be caused by a combination of genetic, biological, environmental, and psychological factors. Proper diagnosis and treatment, which may include psychotherapy, medication, or a combination of both, are essential for managing these conditions and improving quality of life.

The term "DNA, neoplasm" is not a standard medical term or concept. DNA refers to deoxyribonucleic acid, which is the genetic material present in the cells of living organisms. A neoplasm, on the other hand, is a tumor or growth of abnormal tissue that can be benign (non-cancerous) or malignant (cancerous).

In some contexts, "DNA, neoplasm" may refer to genetic alterations found in cancer cells. These genetic changes can include mutations, amplifications, deletions, or rearrangements of DNA sequences that contribute to the development and progression of cancer. Identifying these genetic abnormalities can help doctors diagnose and treat certain types of cancer more effectively.

However, it's important to note that "DNA, neoplasm" is not a term that would typically be used in medical reports or research papers without further clarification. If you have any specific questions about DNA changes in cancer cells or neoplasms, I would recommend consulting with a healthcare professional or conducting further research on the topic.

Colorectal neoplasms refer to abnormal growths in the colon or rectum, which can be benign or malignant. These growths can arise from the inner lining (mucosa) of the colon or rectum and can take various forms such as polyps, adenomas, or carcinomas.

Benign neoplasms, such as hyperplastic polyps and inflammatory polyps, are not cancerous but may need to be removed to prevent the development of malignant tumors. Adenomas, on the other hand, are precancerous lesions that can develop into colorectal cancer if left untreated.

Colorectal cancer is a malignant neoplasm that arises from the uncontrolled growth and division of cells in the colon or rectum. It is one of the most common types of cancer worldwide and can spread to other parts of the body through the bloodstream or lymphatic system.

Regular screening for colorectal neoplasms is recommended for individuals over the age of 50, as early detection and removal of precancerous lesions can significantly reduce the risk of developing colorectal cancer.

Genetic predisposition to disease refers to an increased susceptibility or vulnerability to develop a particular illness or condition due to inheriting specific genetic variations or mutations from one's parents. These genetic factors can make it more likely for an individual to develop a certain disease, but it does not guarantee that the person will definitely get the disease. Environmental factors, lifestyle choices, and interactions between genes also play crucial roles in determining if a genetically predisposed person will actually develop the disease. It is essential to understand that having a genetic predisposition only implies a higher risk, not an inevitable outcome.

Double-stranded DNA breaks (DSBs) refer to a type of damage that occurs in the DNA molecule when both strands of the double helix are severed or broken at the same location. This kind of damage is particularly harmful to cells because it can disrupt the integrity and continuity of the genetic material, potentially leading to genomic instability, mutations, and cell death if not properly repaired.

DSBs can arise from various sources, including exposure to ionizing radiation, chemical agents, free radicals, reactive oxygen species (ROS), and errors during DNA replication or repair processes. Unrepaired or incorrectly repaired DSBs have been implicated in numerous human diseases, such as cancer, neurodegenerative disorders, and premature aging.

Cells possess several mechanisms to repair double-stranded DNA breaks, including homologous recombination (HR) and non-homologous end joining (NHEJ). HR is a more accurate repair pathway that uses a homologous template, typically the sister chromatid, to restore the original DNA sequence. NHEJ, on the other hand, directly ligates the broken ends together, often resulting in small deletions or insertions at the break site and increased risk of errors. The choice between these two pathways depends on various factors, such as the cell cycle stage, the presence of nearby breaks, and the availability of repair proteins.

In summary, double-stranded DNA breaks are severe forms of DNA damage that can have detrimental consequences for cells if not properly repaired. Cells employ multiple mechanisms to address DSBs, with homologous recombination and non-homologous end joining being the primary repair pathways.

Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific regions of DNA. It enables the production of thousands to millions of copies of a particular DNA sequence in a rapid and efficient manner, making it an essential tool in various fields such as molecular biology, medical diagnostics, forensic science, and research.

The PCR process involves repeated cycles of heating and cooling to separate the DNA strands, allow primers (short sequences of single-stranded DNA) to attach to the target regions, and extend these primers using an enzyme called Taq polymerase, resulting in the exponential amplification of the desired DNA segment.

In a medical context, PCR is often used for detecting and quantifying specific pathogens (viruses, bacteria, fungi, or parasites) in clinical samples, identifying genetic mutations or polymorphisms associated with diseases, monitoring disease progression, and evaluating treatment effectiveness.

A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair. DNA repair defects can ... DNA repair, Mutation, DNA replication and repair-deficiency disorders, Causes of conditions, Senescence). ... Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: ... "Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease". DNA Repair (Amst.). 10 (7): 781-91. doi:10.1016/j. ...
Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be ... Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is ... See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in ... "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder". Cell. 99 ...
Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be ... Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is ... See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in ... "An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in ...
2008). "Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and ... WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication. Since WRNp's function depends on DNA, it ... There are three excision repair pathways: nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair ... Cleaver, JE (2005). "Cancer in xeroderma pigmentosum and related disorders of DNA repair". Nature Reviews. Cancer. 5 (7): 564- ...
DNA replication and repair-deficiency disorders). ... interacts with MLH1 but is not required for DNA mismatch repair ... The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ... In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an ... Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at ...
... see article DNA repair-deficiency disorder) are at increased risk of cancer. Some germline mutations in DNA repair genes cause ... Deficiencies in DNA repair cause increased mutation rates. A deficiency in DNA repair, itself, can allow DNA damages to ... and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA ... In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also ...
DNA replication and repair-deficiency disorders, Syndromes). ... These genes code for DNA mismatch repair genes, and mutations ... Routine immunohistochemical detection of DNA mismatch repair proteins help identify hereditary DNA mismatch repair deficiency. ... 2009). "Towards identification of hereditary DNA mismatch repair deficiency: sebaceous neoplasm warrants routine ... The genes affected are MLH1, MSH2, and more recently, MSH6, and are involved in DNA mismatch repair. Muir-Torre syndrome is ...
DNA replication and repair-deficiency disorders, Rare syndromes, Syndromes affecting the skin, Syndromes affecting the eye, ... DeSanctis-Cacchione syndrome is a genetic disorder characterized by the skin and eye symptoms of xeroderma pigmentosum (XP) ...
... imbalance Metabolic brain diseases Disorders of calcium metabolism DNA repair-deficiency disorders Glucose metabolism disorders ... Inherited metabolic disorders are one cause of metabolic disorders, and occur when a defective gene causes an enzyme deficiency ... Specific blood and DNA tests can be done to diagnose genetic metabolic disorders. The gut microbiota, which is a population of ... Metabolic disorder screening can be done in newborns via blood, skin, or hearing tests. Metabolic disorders can be treatable by ...
Neurological disorders, Syndromes affecting the nervous system, Genodermatoses, DNA replication and repair-deficiency disorders ... The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not ... The premature aging features of CS are likely due, at least in part, to the deficiencies in DNA repair (see DNA damage theory ... Each lesion-a damaged section of DNA-must be snipped out and the DNA repaired to preserve its normal function. Unrepaired DNA ...
Autosomal recessive disorders, DNA replication and repair-deficiency disorders, Genodermatoses, Hereditary cancers, Progeroid ... are caused by mutations in genes that repair damaged DNA. XP affects the mechanism that repairs UV damage in skin cell DNA. ... Since DNA repair is under genetic control, it can mutate. Many genetic disorders such as xeroderma pigmentosum (XP; MIM 278700 ... Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused ...
Autosomal recessive disorders, Aplastic anemias, DNA replication and repair-deficiency disorders). ... They are involved in the recognition and repair of damaged DNA; genetic defects leave them unable to repair DNA. The FA core ... a small protein that combines with BRCA2 in another cluster to repair DNA (see Figure Recombinational repair of DNA double- ... Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA ...
Autosomal recessive disorders, Rare diseases, Syndromes with tumors, DNA replication and repair-deficiency disorders, Syndromes ... Mismatch repair cancer syndrome (MMRCS) is a cancer syndrome associated with biallelic DNA mismatch repair mutations. It is ... Under the name constitutional mismatch repair-deficiency, (CMMR-D), it has been mapped to MLH1, MSH2, MSH6 or PMS2. Monoallelic ... Wimmer K, Etzler J (September 2008). "Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of ...
Autosomal recessive disorders, Congenital disorders, Rare diseases, Syndromes, DNA replication and repair-deficiency disorders ... All photosensitive TTD syndromes have defects in the nucleotide excision repair (NER) pathway, which is a vital DNA repair ... Trichothiodystrophy view from the molecular basis of DNA repair transcription factor TF11H.www.oxfordjournals.org/content/18/R2 ... DNA Repair. 9 (1): 2-10. doi:10.1016/j.dnarep.2009.10.005. PMID 19931493. James, William; Berger, Timothy; Elston, Dirk (2005 ...
DNA, Mutation, Dimers (chemistry), DNA replication and repair-deficiency disorders, Senescence, Cyclobutanes). ... In humans, the most common form of DNA repair is nucleotide excision repair (NER). In contrast, organisms such as bacteria can ... One specific translesion DNA polymerase, DNA polymerase η, is deficient in individuals with XPD. Direct DNA damage is reduced ... "DNA Repair". The Cell: A Molecular Approach (2nd ed.). Sinauer Associates. Kemp MG, Sancar A (August 2012). "DNA excision ...
Congenital disorders, Rare diseases, DNA replication and repair-deficiency disorders, Telomeropathies, Progeroid syndromes). ... DNA polymerase can only synthesize new DNA from an old DNA strand in the 5'→3' direction. Given that DNA has two strands that ... As DNA polymerase requires RNA primers for DNA binding in order to commence replication, each Okazaki fragment is thus preceded ... Telomeres are placed by telomerase on both ends of linear chromosomes as a way to protect linear DNA from general forms of ...
For example, individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder ... In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also ... this causes a DNA repair deficiency. This is shown in the figure at the 4th level from the top. With a DNA repair deficiency, ... In sporadic cancers, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene; much more frequently, ...
DNA replication and repair-deficiency disorders, Progeroid syndromes, Syndromes affecting stature, Syndromes affecting bones, ... WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication. Specifically, it has an important role in ... Accelerated aging disease Biogerontology Cockayne syndrome DNA repair Degenerative disease Genetic disorder Life extension ... Bernstein KA, Gangloff S, Rothstein R (2010). "The RecQ DNA helicases in DNA repair". Annu. Rev. Genet. 44: 393-417. doi: ...
Autosomal recessive disorders, DNA replication and repair-deficiency disorders, Genodermatoses, Rare diseases, Syndromes ... nucleotide excision repair and base excision repair. The association of deficient RECQL4-mediated DNA repair with accelerated ... "RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks". Cell Rep. 16 (1): 161-73. doi:10.1016/j.celrep. ... RECQL4 also appears to be necessary for other forms of DNA repair including non-homologous end joining, ...
Autosomal recessive disorders, Rare syndromes, Syndromes affecting bones, DNA replication and repair-deficiency disorders, ... The RECQL4 protein is involved in DNA replication and repair as well as the stability of genetic information in cells. The most ... In the lack of helicase function, normal DNA replication and repair may be impaired resulting in widespread genetic damage. ... Helicases are enzymes that temporarily bind to DNA and unwind the DNA molecule's two spiral strands. This unwinding is needed ...
Neurodegenerative disorders, IUIS-PID table 3 immunodeficiencies, DNA replication and repair-deficiency disorders, Syndromes ... a DNA repair disorder and a DNA damage response (DDR) syndrome. ATM, the gene responsible for this multi-system disorder, ... "Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia". DNA Repair. 13: 22-31. doi:10.1016/j.dnarep.2013.11.002. ... Thus, ATM allows the cell to repair its DNA before the completion of cell division. If DNA damage is too severe, ATM will ...
DNA replication and repair-deficiency disorders, Autosomal recessive disorders, Rare syndromes, Syndromes affecting stature, ... DNA repair mechanism and/or the synthesis dependent strand annealing mechanism for repairing double strand breaks in DNA (see ... when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of DNA repair. This ... "Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder". American Journal of Human Genetics. 84 (5): 605-16. doi: ...
DNA replication and repair-deficiency disorders, Colorectal cancer, Hereditary cancers, Syndromes with tumors, Syndromes ... Bellizzi AM, Frankel WL (November 2009). "Colorectal cancer due to deficiency in DNA mismatch repair function: a review". ... Mutations in DNA mismatch repair systems can lead to difficulty transmitting regions within the DNA which contain repeating ... which coordinates the binding of other proteins involved with mismatch repair like DNA helicase, single-stranded-DNA binding- ...
DNA replication and repair-deficiency disorders, Genetic disorders by system, Noninfectious immunodeficiency-related cutaneous ... Some SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not diagnosed ... However, carriers, who themselves are not affected by the disease, can be detected with a DNA test. Therefore, careful breeding ... Anne Esguerra, Z; Watanabe, G; Okitsu, CY; Hsieh, CL; Lieber, MR (April 2020). "DNA-PKcs chemical inhibition versus genetic ...
DNA replication and repair-deficiency disorders, Progeroid syndromes, Syndromes with tumors, Syndromes affecting stature, ... DNA helicases function in DNA replication and DNA repair. BLM very likely functions in DNA replication, as cells from persons ... at nucleoli DNA helicases are enzymes that attach to DNA and temporarily unravel the double helix of the DNA molecule. ... Human BLM cells are sensitive to DNA damaging agents such as UV and methyl methanesulfonate, indicating deficient repair ...
DNA replication and repair-deficiency disorders, Hereditary cancers, Rare diseases, Single-nucleotide polymorphism associated ... DNA damage information can be conveyed to p53 to indirectly arrest the cell cycle at that point for DNA repair to be able to ... The repair of "bad" DNA, or the apoptosis of a cell, prevents the proliferation of damaged cells.[citation needed] Mutant ... LFS fibroblast cells that are homozygous for TP53 mutations are deficient in global nucleotide excision repair of DNA and have ...
... see DNA repair-deficiency disorder). In bacteria, transformation is a process of gene transfer that ordinarily occurs between ... Boyd JB (1978). "DNA repair in Drosophila". In Hanawalt PC, Friedberg EC, Fox CF (eds.). DNA Repair Mechanisms. New York: ... It is a process by which a DNA sequence is copied from one DNA helix (which remains unchanged) to another DNA helix, whose ... can be repaired by homologous recombinational repair (HRR). These findings suggest that DNA damages arising from natural ...
... see DNA repair-deficiency disorder). On the other hand, the ability to trigger apoptosis in the presence of excess un-repaired ... Ageing Aging brain AP site Direct DNA damage DNA DNA adduct DNA damage theory of aging DNA repair DNA replication Free radical ... While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non- ... At least 17 DNA repair proteins, distributed among five DNA repair pathways, have a "dual role" in response to DNA damage. With ...
Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have an ... Human DNA Repair Genes 3D structures of some DNA repair enzymes Human DNA repair diseases DNA repair special interest group DNA ... Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at ... Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are ...
Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be ... homologous recombinational repair, and DNA mismatch repair. PARP1 has a role in repair of single-stranded DNA (ssDNA) breaks. ... Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is ... and by interacting with and modifying multiple DNA repair factors. PARP1 is implicated in the regulation of several DNA repair ...
A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair. DNA repair defects can ... DNA repair, Mutation, DNA replication and repair-deficiency disorders, Causes of conditions, Senescence). ... Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: ... "Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease". DNA Repair (Amst.). 10 (7): 781-91. doi:10.1016/j. ...
Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause the dominant adult cancer ... DNA Repair-Deficiency Disorders / etiology* * DNA Repair-Deficiency Disorders / genetics * DNA Repair-Deficiency Disorders / ... Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? Hum Genet. 2008 Sep;124(2): ... Alluding to the underlying mechanism, this condition may be termed as "constitutional mismatch repair-deficiency (CMMR-D) ...
Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and ... which impairs both DNA repair and gene transcription. An inability to repair DNA damage probably underlies the sun sensitivity ... Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development. Clin Genet. 2010 ... DNA Repair (Amst). 2008 May 3;7(5):744-50. doi: 10.1016/j.dnarep.2008.01.014. Epub 2008 Mar 10. Citation on PubMed ...
These diseases are disorders of the hematopoietic stem cell that can involve either 1 cell line or all of the cell lines ( ... The bone marrow failure syndromes include a group of disorders than can be either inherited or acquired. ... ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). [9] ... These genes collaborate in a complicated pathway (FA pathway) that is responsible for the repair of DNA damage. One of these ...
... our understanding of development of lymphoid malignancy in children with inherited immune deficiency or DNA repair disorders ... Understanding and Future Research Priorities in Malignancy Associated With Inborn Errors of Immunity and DNA Repair Disorders: ... Recommendations for the Clinical Management of Hematological Malignancies in Patients with DNA Double Stranded Break Disorders ... HSCT provides effective treatment for lymphoproliferative disorders in children with primary immunodeficiency. Journal of ...
DNA Repair-Deficiency Disorders Medicine & Life Sciences 100% * Xeroderma Pigmentosum Medicine & Life Sciences 91% ... Dive into the research topics of Mutation spectra induced by α-acetoxytamoxifen-DNA adducts in human DNA repair proficient and ... Mutation spectra induced by α-acetoxytamoxifen-DNA adducts in human DNA repair proficient and deficient (Xeroderma pigmentosum ... Mutation spectra induced by α-acetoxytamoxifen-DNA adducts in human DNA repair proficient and deficient (Xeroderma pigmentosum ...
"DNA-repair defects" or "DNA-repair deficiency" disorders. The ATM (Ataxia-telangiectasia mutated kinase) gene mutated in AT is ... A rare case of ataxia-telangiectasia-like disorder with MRE11 mutation. Rohan R Mahale, Nishanth Reddy, Pavagada Mathuranth, ... The prototypical disorder for the early-onset cerebellar ataxia with cerebellar atrophy is ataxia telangiectasia (AT). AT ... A rare case of ataxia-telangiectasia-like disorder with MRE11 mutation. J Pediatr Neurosci [serial online] 2020 [cited 2023 Dec ...
DNA Repair-Deficiency Disorders Medicine & Life Sciences 100% * Atlases Medicine & Life Sciences 73% ... Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. Cell reports. 2018 Apr 3;23(1): ... Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. In: Cell reports. 2018 ; Vol. ... Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. / The Cancer Genome Atlas ...
DNA Repair-Deficiency Disorders; Colorectal Neoplasms; Urologic Neoplasms; Microsatellite Instability; Lymphoma, T-Cell, ... Microsatellite instability-high cancer; Mismatch Repair Deficient Cancer. Lepu Biotech Co Ltd. 2022-07-19. Solid tumours; ... GMP grade cytokines, reagents for cell activation, gene edition, DNA/RNA removal, etc. Particularly focus on product design, ... Mismatch Repair Deficient Cancer; Skin Melanoma; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell, Peripheral; Leukemia; Liver ...
DNA Repair-Deficiency Disorders 11% * Nucleic Acid Synthesis Inhibitors 10% * Cricetulus 8% ... Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells. Luis Francisco Zirnberger Batista, Vanessa ... Dive into the research topics of Involvement of DNA replication in ultraviolet-induced apoptosis of mammalian cells. Together ...
Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. The Cancer Genome Atlas ... DNA Repair-Deficiency Disorders 100% * Atlases 73% * DNA Damage 59% * Mutation 57% ...
DNA Repair-Deficiency Disorders 98% * DNA Mismatch Repair 80% * Colorectal Neoplasms 53% ... Clinically important molecular features of Peruvian colorectal tumours: High prevalence of DNA mismatch repair deficiency and ... Cell-free circulating tumor DNA in colorectal cancer: a proof of concept with simplified methodology. Bosque, J., Guirao, C., ...
DNA Repair-Deficiency Disorders [C18.452.284]. *Severe Combined Immunodeficiency [C18.452.284.800]. *Immune System Diseases [ ... Clarridge K, Leitenberg D, Loechelt B, Picard C, Keller M. Major Histocompatibility Complex Class II Deficiency due to a Novel ... Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children with T-B-NK+ immunodeficiency. J Clin Immunol. ... Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low ...
DNA Repair-Deficiency Disorders Medicine & Life Sciences 15% * Adenosine Diphosphate Ribose Medicine & Life Sciences 15% ... An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair ... An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair ... An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair ...
... accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair ... accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair ... accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair ... accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair ...
Based on similar approaches in other neurodegenerative disorders, we propose to validate diagnostic and severity scores for ... Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. This rare ... Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum. Cockayne Syndrome Trichothiodystrophy ... Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. This rare ...
Progressive pancytopenia is a common feature observed in DNA crosslink repair deficiency disorder, Fanconi anemia (FA). However ... Hemolytic disorders are characterized by hemolysis and are prone to thrombosis. It has previously been shown that the RNA ... The mutation was confirmed by DNA sequencing as a termination codon UAA in place of AAA codon at position 886 in the gp1ba ... The tail clips from these fish were used to prepare DNA and sequenced to identify heterozygotes. They were then bred to obtain ...
DNA 46% * Turcot syndrome 45% * DNA Repair-Deficiency Disorders 44% 118 Scopus citations ... DNA repair , DNA mismatch repair and the DNA damage response. Xu, W. & Li, G. M., Jul 29 2021, Encyclopedia of Biological ... DNA-PK is activated by SIRT2 deacetylation to promote DNA double-strand break repair by non-homologous end joining. Head, P. S ... DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity. Lu, C., Guan, J., Lu, S., Jin, Q., ...
All MeSH CategoriesDiseases CategoryNutritional and Metabolic DiseasesMetabolic DiseasesDNA Repair-Deficiency DisordersAtaxia ... Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein ... All MeSH CategoriesDiseases CategoryImmune System DiseasesImmunologic Deficiency SyndromesPrimary Immunodeficiency Diseases ... An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ...
We report two patients with DNA repair disorders (Artemis deficiency, Ataxia telangiectasia) with destructive skin granulomas, ... Rubella Virus-Induced Cutaneous Granulomas in Two Pediatric Patients With DNA Double Strand Breakage Repair Disorders - Outcome ... newborn screening may help to prevent patients with moderate T-cell deficiency from receiving live-attenuated rubella vaccine ...
Pigmentation disorders, Template:DNA replication and repair-deficiency disorder ... B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, ... v · Cell membrane protein disorders (other than Cell surface receptor, enzymes, and cytoskeleton). ...
... can lead to genetic disorders that impair physical and mental abilities such as microcephaly or DNA repair-deficiency disorders ... Life sciences have been greatly influenced by the progress of DNA sequencing technologies. The field of Evolutionary Biology is ... Main topics of this course include genetic disorders that are related to mechanisms of cell division and are discussed using ... no exception, and increasingly relies upon fast generation of DNA sequences, that are analysed using fast evolving ...
... to explore gene expression changes in rare DNA repair-deficiency disorders. The analysis uncovered a scaffolding protein ( ... CEP135) important in cell division that was depleted in DNA repair diseases with a high predisposition for cancers. Stratifying ...
Calcium Metabolism Disorders. DNA Repair-Deficiency Disorders. Glucose Metabolism Disorders. Diabetes Mellitus ...
Abstract Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. ... DNA repair deficiency in neurodegeneration. Jeppesen DK, Bohr VA, Stevnsner T. SourceDanish Centre for Molecular Gerontology ... Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many ... DNA repair deficiency in neurodegeneration.. Jeppesen DK, Bohr VA, Stevnsner T.. SourceDanish Centre for Molecular Gerontology ...
DNA Repair-Deficiency Disorders [C18.452.284] DNA Repair-Deficiency Disorders * Glucose Metabolism Disorders [C18.452.394] ...
Total immunoglobulin A deficiency (IgAD) is defined as an undetectable serum immunoglobulin A (IgA) level at a value < 5 mg/dL ... is a primary immunodeficiency disease and is the most common of the primary antibody deficiencies. ... is a particularly notable aspect of ataxia-telangiectasia and related disorders in which mutations in DNA processing/repair ... High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes. ...
The DNA repair field is a vibrant one, and the stage is ripe for scrutinizing the potential treatment efficacy and future ... Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well ... However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also ... The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and ...
This article belongs to the Special Issue DNA Damage and Repair in Plants). ... are highlighted by the fact that deficiencies in the respective pathways are associated with diverse hereditary disorders. Full ... DNA-crosslinks are one of the most severe types of DNA lesions. Crosslinks (CLs) can be subdivided into DNA-intrastrand CLs, ... DNA-crosslinks are one of the most severe types of DNA lesions. Crosslinks (CLs) can be subdivided into DNA-intrastrand CLs, ...
  • Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. (wikipedia.org)
  • Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table. (wikipedia.org)
  • Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause the dominant adult cancer syndrome termed Lynch syndrome or hereditary non-polyposis colorectal cancer. (nih.gov)
  • Amegakaryocytic thrombocytopenia is an autosomal recessive disorder with biallelic mutations in the thrombopoietin receptor, MPL, at the band 1p34 location. (medscape.com)
  • Relative mutation frequencies increased with the adduct level, with 1.3-3.6-fold higher numbers of mutations in the XP cells compared to the GM00637 cells, indicating that NER plays a significant role in the removal of these particular tamoxifen DNA adducts. (mssm.edu)
  • Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). (johnshopkins.edu)
  • IgA deficiency is a particularly notable aspect of ataxia-telangiectasia and related disorders in which mutations in DNA processing/repair mechanisms interfere with rearrangements of immunoglobulin and T-cell receptor genes. (medscape.com)
  • These 2 syndromes, AT and NBS, are part of a family of mutations involving proteins involved in DNA repair. (medscape.com)
  • Artemis deficiency (with mutations in the Artemis protein resulting in defective VDJ recombination) decreases both T cells and B cells and can be considered part of a subset of SCIDs. (medscape.com)
  • Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging. (lookformedical.com)
  • BML mutations thus result in defects in DNA repair and genomic instability in the somatic cells, predisposing the patients to cancer development. (medscape.com)
  • Diseases and disorders can be associated with misspellings or genetic mutations. (bvsalud.org)
  • In addition, chemotherapeutic drugs that inhibit DNA synthesis can result in findings similar to those seen in cobalamin or folate deficiency. (mhmedical.com)
  • Folic acid, or folate, deficiency is a serious condition that needs to be treated rapidly. (product-managers.com)
  • At first, a person may not have obvious symptoms of folate deficiency anemia, but as it becomes more severe, people may notice: Signs of folate deficiency are often subtle. (product-managers.com)
  • You may be at a greater risk of folate deficiency if you are pregnant, or have Chrohn's disease or celiac disease. (product-managers.com)
  • FOLATES are water-soluble vitamins in the vitamin B group and are found in food in fruit, fresh vegetables, and corn products ().Insufficient food intake of folate is a common cause of low folate levels ().Elderly people are shown to have increased risk of low folates, but there are no exact figures on the prevalence or incidence of folate deficiency (3, 4). (product-managers.com)
  • Folate deficiency symptoms can include tongue inflammation, mouth sores, and fatigue. (product-managers.com)
  • WebMD explains the complications of folate deficiency. (product-managers.com)
  • Folic acid is also used for other conditions commonly associated with folate deficiency, including ulcerative colitis, liver disease, alcoholism, and kidneydialysis. (product-managers.com)
  • Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? (nih.gov)
  • Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby causing Huntington's disease. (clubalthea.com)
  • MSI testing detects DNA mismatch repair (MMR) deficiency in tumor tissue. (propath.com)
  • The bone marrow failure syndromes comprise a group of disorders than can be either inherited or acquired. (medscape.com)
  • The inherited bone marrow failure syndromes (IBMFS) include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and other genetic disorders. (medscape.com)
  • Throughout the lifetime of patients with an FA gene mutation, DNA damage increasing accumulates, which would lead to a complex clinically and genetically heterogeneous disorder characterized by developmental abnormalities, bone marrow failure (BMF), immune deficiency, and a high risk of developing various cancers (e.g. (frontiersin.org)
  • Both diseases show phenotypical similarity and both demonstrate bone marrow failure, skeletal growth deficiency, short stature, and predisposition to hematological malignancies, although they are genetically unrelated. (medscape.com)
  • When a mutation is present in a DNA repair gene, the repair gene will either not be expressed or be expressed in an altered form. (wikipedia.org)
  • Shwachman-Diamond syndrome is an autosomal recessive disorder in which the majority of patients have a mutation in the Shwachman Bodian Diamond syndrome gene ( SBDS ), located at band 7q11. (medscape.com)
  • Mutation of this gene results in ataxia-telangiectasia-like disorder (ATLD). (pediatricneurosciences.com)
  • Clarridge K, Leitenberg D, Loechelt B, Picard C, Keller M. Major Histocompatibility Complex Class II Deficiency due to a Novel Mutation in RFXANK in a Child of Mexican Descent. (ctsicn.org)
  • Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. (clubalthea.com)
  • Ataxialike disorder (ATLD) syndrome involves a mutation in meiotic recombination 11 homolog (MRE11). (medscape.com)
  • Patients with FA gene mutation are hypersensitive to DNA damage and unable to successfully repair damaged DNA when exposed to DNA-crosslinking agents, cytotoxic chemotherapeutics, and ionizing radiation ( 3 , 4 ). (frontiersin.org)
  • Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. (lookformedical.com)
  • An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair proteins (e.g. (elsevierpure.com)
  • During NHEJ, once a DSB is formed the broken ends are bound by Ku proteins (ku70 and ku80), which form a heterodimer and insulate the DNA ends from nucleolytic erosion [ 11 , 12 ]. (springeropen.com)
  • The Ku proteins foster direct ligation of the broken DNA ends by the specialized ligase complex Dnl4-Lif1 [ 12 ]. (springeropen.com)
  • Deficiency of the expression of major histocompatibility complex (MHC) class I and II cellular proteins also commonly manifests in early infancy with classic symptoms of SCID. (medscape.com)
  • One of the most versatile defense mechanisms against the accumulation of DNA damage is nucleotide excision repair, in which, among others, the Xeroderma pigmentosum group C (XPC) and group A (XPA) proteins are involved. (aacrjournals.org)
  • Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. (lookformedical.com)
  • B12 assists in the transformation of proteins in the body, supporting muscle repair and growth. (detoxvalue.com)
  • Ataxia-telangiectasia Bloom syndrome Cockayne syndrome Fanconi anemia Progeria (Hutchinson-Gilford progeria syndrome) Rothmund-Thomson syndrome Trichothiodystrophy Werner syndrome Xeroderma pigmentosum Some examples of DNA repair defects causing progeroid syndromes in humans or mice are shown in Table 1. (wikipedia.org)
  • The prototypical disorder for the early-onset cerebellar ataxia with cerebellar atrophy is ataxia telangiectasia (AT). (pediatricneurosciences.com)
  • The ATM (Ataxia-telangiectasia mutated kinase) gene mutated in AT is central to deoxyribonucleic acid (DNA) damage response (DDR) signaling. (pediatricneurosciences.com)
  • Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. (clubalthea.com)
  • Ataxia-telangiectasia (AT) is a rare, autosomal recessive, neurodegenerative disorder in which the diagnosis is obvious when both ataxia and telangiectasia are present. (medscape.com)
  • An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease. (lookformedical.com)
  • An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. (lookformedical.com)
  • Bloom syndrome (congenital telangiectatic erythema) is a rare autosomal recessive disorder. (medscape.com)
  • DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. (wikipedia.org)
  • Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (often some of both). (wikipedia.org)
  • These diseases are intrinsic disorders of the bone marrow involving disruption in the homeostasis and function of hematopoietic stem cells, resulting in inadequate production of either a single or multiple cell lines (erythroid for red cells, myeloid for white blood cells, megakaryocytic for platelets). (medscape.com)
  • Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. (clubalthea.com)
  • Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. (clubalthea.com)
  • Those diseases are discussed in T-Cell Disorders. (medscape.com)
  • Diseases of the skin associated with underlying metabolic disorders. (nih.gov)
  • NAD+ is important for DNA repair and energy production, and scientists are studying its potential for treating diseases. (longevitybox.co.uk)
  • Both diseases involve the BRAFT and FANCM complexes, which are important in DNA repair. (medscape.com)
  • This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. (medscape.com)
  • Previous studies based on analysis of blood donor banks have suggested that up to 90% of patients with selective immunoglobulin A deficiency (SIgAD) are asymptomatic. (medscape.com)
  • The main cause of megaloblastic anemias is deficiency of either cobalamin (vitamin B 12 ) or folic acid, vitamins that are essential for DNA replication and repair. (mhmedical.com)
  • Despite the high benefits relative to cost, millions of people continue to have vitamin D deficiency. (vitamindwiki.com)
  • The prevalence of vitamin D deficiency increases in countries furthest from the equator. (vitamindwiki.com)
  • However, despite the presence of abundant sunlight, the incidence of vitamin D deficiency is high even among those who live within 1,000 km of the equator, such as the populations of India, Sri Lanka, and Far Eastern, Middle Eastern, and Persian Gulf countries [1-4]. (vitamindwiki.com)
  • However, little is known on the status of use of folic acid and vitamin supplements among people with mental disorders. (product-managers.com)
  • Vitamin B12 and folic acid (FA) deficiencies present with symptoms like anemia and birth defects, but the underlying mechanism remains unclear. (product-managers.com)
  • Vitamin B12 , an essential nutrient, plays a pivotal role in numerous bodily functions, from DNA synthesis to red blood cell formation. (detoxvalue.com)
  • What is a Vitamin B12 Deficiency? (detoxvalue.com)
  • Vitamin B12 deficiency arises when the body lacks enough of this essential nutrient to function optimally . (detoxvalue.com)
  • Cockayne syndrome is a progressive multisystem genetic disorder linked to defective DNA repair and transcription. (biomedcentral.com)
  • Based on similar approaches in other neurodegenerative disorders, we propose to validate diagnostic and severity scores for Cockayne syndrome. (biomedcentral.com)
  • Cockayne syndrome (CS) is an autosomal recessive multisystem disorder characterized by mental retardation, microcephaly, severe growth failure, sensorial impairment, cutaneous photosensitivity, dental anomalies, recognizable facial appearance with enophtalmos [ 1 ]. (biomedcentral.com)
  • See Omenn Syndrome and Purine Nucleoside Phosphorylase Deficiency for a discussion of other forms of SCID. (medscape.com)
  • Among the simple Mendelian disorders of humans, Werner syndrome most closely resembles an acceleration of normal aging. (yale.edu)
  • The series of investigations strongly suggest that defects in DNA repair of specific lesions produced by oxidative damage in slowly dividing or non-dividing cells account for those unique aspects of Werner syndrome that mimic normal aging. (yale.edu)
  • It was originally developed as an aid to help identify if further testing was needed to determine Lynch Syndrome, an inherited genetic disorder that predisposes individuals to developing cancer. (propath.com)
  • The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase. (lookformedical.com)
  • Crystal structure of the Bloom syndrome helicase BLM in complex with DNA (PDB ID: 4CGZ). (medscape.com)
  • [ 16 ] Bloom syndrome patients exhibit a greater vulnerability of their DNA to UV radiation than DNA of healthy populations. (medscape.com)
  • We also propose that over time these DNA lesions would also accumulate in stem/precursor cells impairing their replicative capacity, thereby contributing to the complex aging phenotype. (yale.edu)
  • Deficiencies are highly variable with regard to symptoms, phenotype, genotype, severity, etc, because many cells and molecules are required for both natural and adaptive immunity . (lu.se)
  • Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. (medscape.com)
  • Deficiency of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) elevates intracellular levels of deoxyguanosine and deoxyadenosine, respectively. (medscape.com)
  • MCM8- and MCM9 Deficiencies Cause Lifelong Increased Hematopoietic DNA Damage Driving p53-Dependent Myeloid Tumors. (nih.gov)
  • Also see the "DNA damage theory of aging" for a discussion of the evidence that DNA damage is the primary underlying cause of aging. (wikipedia.org)
  • Biogerontology Degenerative disease DNA damage theory of aging Genetic disorder Senescence Park JM, Kang TH (2016). (wikipedia.org)
  • This complex is involved in the repair of DNA damage, which can be caused by UV rays. (medlineplus.gov)
  • An inability to repair DNA damage probably underlies the sun sensitivity in affected individuals. (medlineplus.gov)
  • These genes collaborate in a complicated pathway (FA pathway) that is responsible for the repair of DNA damage. (medscape.com)
  • DNA adducts have been detected at low levels in human endometrium, and there is much interest in determining whether DNA damage plays a role in tamoxifen-induced endometrial carcinogenesis. (mssm.edu)
  • DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. (elsevierpure.com)
  • present The Cancer Genome Atlas (TCGA) Pan-Cancer analysis of DNA damage repair (DDR) deficiency in cancer. (elsevierpure.com)
  • The Cancer Genome Atlas Research Network 2018, ' Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas ', Cell reports , vol. 23, no. 1, pp. 239-254.e6. (elsevierpure.com)
  • Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. (clubalthea.com)
  • Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. (clubalthea.com)
  • Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)
  • In this way, CoQ10 helps protect cells from the harmful effects of DNA damage. (medicalnewstoday.com)
  • For this patient, we hypothesized that an altered FA pathway resulted in genomic instability, hypersensitivity to DNA-crosslinking agents or cytotoxic chemotherapeutics, and unsuccessful DNA damage repair. (frontiersin.org)
  • The accumulation of DNA damage is a slow but hazardous phenomenon that may lead to cell death, accelerated aging, and cancer. (aacrjournals.org)
  • Damage can often be repaired (DNA REPAIR). (lookformedical.com)
  • Idiopathic Pulmonary Fibrosis (IPF), the most severe interstitial lung disease, is a devastating condition characterized by deregulation of tissue repair processes subsequent to lung tissue damage. (univ-orleans.fr)
  • Melanogenesis: a photo- epidemiological study on sunbed use and cuta- protective response to DNA damage? (who.int)
  • They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores. (elsevierpure.com)
  • The main pathway for repairing oxidative base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. (clubalthea.com)
  • Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)
  • A second NHEJ concomitant pathway often referred to as alternative-NHEJ (Alt-NHEJ), also known as Microhomology-mediated end joining (MMEJ), is another well-studied pathway for repairing DSBs in DNA [ 16 ]. (springeropen.com)
  • The Fanconi anemia (FA) pathway (also known as the FA-BRCA pathway) is involved in the repair of DNA lesions by homologous recombination, which plays a vital role in the maintenance of genomic stability ( 1 ). (frontiersin.org)
  • Regardless of the etiology, a deficiency of cyclooxygenase (COX), a key regulatory enzyme in the synthetic pathway of eicosanoid production, results in beneficial and detrimental physiologic conditions relative to imbalances of the eicosanoids. (medscape.com)
  • [ 1 ] Thus, tracing research of the COX pathway is essential to an understanding of COX deficiency, and examining the variable effects of COX inhibition are advantageous. (medscape.com)
  • Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)
  • My research interest focuses on how genes and genetic mechanisms contribute to childhood developmental or late-onset disorders of the human nervous system. (yale.edu)
  • 1. Exploitation of rare genetic disorders with Mendelian trait may provide novel insights into mechanisms of common disorders and complex biological processes, such as dementia, diabetes or aging, and recognized disease pathways can offer strategies for prevention, diagnosis, and therapy. (yale.edu)
  • CS is related to defective DNA repair and transcription processes and belongs to the family of Nucleotide Excision Repair (NER) disorders together with xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) [ 3 ]. (biomedcentral.com)
  • Variants in the ERCC2 , ERCC3 , or GTF2H5 genes reduce the amount of TFIIH complex within cells, which impairs both DNA repair and gene transcription. (medlineplus.gov)
  • Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. (elsevierpure.com)
  • Fanconi anemia (FA) genes play critical roles in the repair of DNA lesions. (frontiersin.org)
  • Recovery of RNA synthesis (RRS, decreased in CS) and unscheduled DNA synthesis (UDS, normal in CS) are the classical gold standard functional assays which are used to ascertain the diagnosis in cultured fibroblasts [ 4 ]. (biomedcentral.com)
  • In the megaloblastic anemias, DNA synthesis is impaired, leading to slowing or arrest of cellular division during the DNA synthesis phase of the cell cycle (S phase). (mhmedical.com)
  • B12 plays a role in DNA synthesis, which is crucial for the formation of new cells. (detoxvalue.com)
  • B12 plays a significant role in DNA synthesis, which is fundamental for cell division and repair. (detoxvalue.com)
  • B12 is crucial for processes like red blood cell formation and DNA synthesis, and its deficiency can lead to anemia and neurological complications. (detoxvalue.com)
  • Individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer. (wikipedia.org)
  • Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. (ctsicn.org)
  • When T-cell deficiency is especially severe or involves the T-helper cell function, the deficiency causes an antibody deficiency. (medscape.com)
  • 1) Antibody deficiency disorders are defects in immunoglobulin-producing B cells . (lu.se)
  • 3) T cell deficiencies result usually in combined immunodeficiencies (CIDs), where both T cells and antibody production are defective. (lu.se)
  • Patients with antibody deficiencies are especially susceptible to encapsulated bacteria, which cause pyogenic infections. (lu.se)
  • Antibody deficiencies are treated with intravenous immunoglobulin substitution therapy. (lu.se)
  • The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). (springeropen.com)
  • Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored. (springeropen.com)
  • DNA double strand breaks (DSBs) result as a consequence of the disassembly of the DNA double helix leading to the disruption of the stability of the genome. (springeropen.com)
  • Regardless of how DSBs are formed, faithful repair of these breaks are absolutely essential for maintenance of genome integrity. (springeropen.com)
  • Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)
  • A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. (lookformedical.com)
  • [ 7 , 8 ] Sister chromatid exchanges are considered a sensitive indicator for cell genome instability, as they are thought to be the outcome of DNA double-strand breaks resulting from homologous recombination repair. (medscape.com)
  • The protein produced from the MPLKIP gene does not appear to be involved in DNA repair. (medlineplus.gov)
  • pSP189 plasrnid DNA containing the supF gene was treated with α-acetoxytamoxifen and adduct levels (0.5-8.0 adducts per plasmid) determined by 32 P-postlabeling. (mssm.edu)
  • Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23). (beds.ac.uk)
  • To define better cellular events that are specifically vulnerable to WRN deficiency, I used RNA interference (RNAi) to silence the expression of Wrn gene and other RecQ helicases, linked to different clinical phenotypes, in primary human fibroblasts. (yale.edu)
  • Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. (medscape.com)
  • Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. (medscape.com)
  • DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. (clubalthea.com)
  • In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration. (clubalthea.com)
  • The two most commonly used pathways to repair DSBs in higher eukaryotes include non-homologous end joining (NHEJ) and homologous recombination (HR). NHEJ is considered to be error-prone, intrinsically mutagenic quick fix remedy to seal together the broken DNA ends and restart replication. (springeropen.com)
  • DNA double strand break repair (DSBR) pathways are generally classified based on whether sequence homology is used to join the broken DNA ends. (springeropen.com)
  • In certain metabolic disorders ( ADA and PNP deficiency) enzyme substitution therapy can be applied. (lu.se)
  • Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. (johnshopkins.edu)
  • Iron deficiency anemia (IDA) is the most common hematologic disorder in the United States and worldwide. (bcm.edu)
  • are the most common hematologic disorders diagnosed at birth. (msdmanuals.com)
  • DNA repair deficiency in neurodegeneration. (clubalthea.com)
  • Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive neurodegeneration. (clubalthea.com)
  • Here are 5 symptoms of folic acid deficiency in adults. (product-managers.com)
  • A folic acid deficiency causes a variety of symptoms triggered by a decrease in the amount of oxygen in your body. (product-managers.com)
  • This article highlights the signs and symptoms to identify this deficiency in our body. (product-managers.com)
  • Two autosomal recessive syndromes involving DNA repair indicate some interaction between the immune system and neurologic function. (medscape.com)
  • Funk and co-investigators localized COX-1 to 9q32-q33.3 via somatic hybrid deoxyribonucleic acid (DNA) analysis. (medscape.com)
  • Predicted to contribute to single-stranded DNA helicase activity. (nih.gov)
  • This protein plays a pivotal role in DNA recombination and repair. (medscape.com)
  • Orthologous to human MCM8 (minichromosome maintenance 8 homologous recombination repair factor). (nih.gov)
  • The incidence of PIDs varies greatly from about 1:500 births with selective IgA deficiency to only a few known cases for the rarest disorders. (lu.se)
  • Adducted plasmids were transfected into nucleotide excision repair proficient (GM00637) or deficient (GM04429, XPA) human fibroblasts. (mssm.edu)
  • Folic acid deficiency means that there is a lower than normal amount of folic acid in your blood. (product-managers.com)
  • Related article: 7 Reasons To Eat Mint Every Day Carotid artery stenosis (leading to strokes) and peripheral vascular disease also appear in high frequency for those with low folic acid level or a folic acid deficiency. (product-managers.com)
  • One folic acid deficiency causes in adults to a disturbed new formation of red blood cells. (product-managers.com)
  • Pathophysiology of Blood Disorders, 2e Aster JC, Bunn H. Aster J.C., & Bunn H(Eds. (mhmedical.com)
  • The iron sulfate that is made from pyrite can be used in the treatment of iron deficiency anemia. (neocrystals.com)
  • Any disruption in this process, such as in pernicious anemia, can lead to B12 deficiency. (detoxvalue.com)
  • for the management of autoimmune and temporomandibular joint disorders. (bvsalud.org)
  • The lymphocytes, which are involved in lymphoproliferative disorders, are usually spared (see the image below). (medscape.com)
  • disorders of the DNA replication machinery. (nih.gov)
  • In prior studies I demonstrated that WRN protein directly interacts with the DNA replication machinery. (yale.edu)
  • DSBs not only ensue from normal cellular metabolism, in the form of reactive oxygen species that can oxidize DNA bases [ 1 , 2 ], but can also be generated during physiological processes like chromosome replication, meiotic recombination and DNA replication transcription collision [ 3 - 7 ]. (springeropen.com)
  • Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. (lookformedical.com)
  • This protein interacts with another protein that is involved in processing and repairing RNA molecules, which are chemical cousins of DNA. (medlineplus.gov)
  • A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. (lookformedical.com)