• As each chromosome contains a single centromere, it remains unclear how acentric fragments derived from shattered chromosomes are inherited between daughter cells during mitosis 6 . (nature.com)
  • Here we tracked micronucleated chromosomes with live-cell imaging and show that acentric fragments cluster in close spatial proximity throughout mitosis for asymmetric inheritance by a single daughter cell. (nature.com)
  • Here we show that pulverized chromosomes from micronuclei spatially cluster throughout mitosis and identify the CIP2A-TOPBP1 complex as an essential regulator of this process. (nature.com)
  • Using single-cell DNA sequencing8 after an error-prone mitosis in untransformed, diploid cell lines and organoids, we show that chromosomes have different segregation error frequencies that result in non-random aneuploidy landscapes. (ox.ac.uk)
  • The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. (nih.gov)
  • The maintenance of a single centromere per chromosome is critical for establishing bipolar microtubule attachments to the mitotic spindle and achieving high-fidelity genome segregation 17 . (nature.com)
  • We herein report that oocyte-specific Uhrf1 KO results in impaired chromosome segregation, abnormal cleavage division, and preimplantation lethality of derived embryos. (life-science-alliance.org)
  • An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional. (lookformedical.com)
  • Nuclear chromosome locations dictate segregation error frequencies. (ox.ac.uk)
  • Chromosome segregation errors during cell divisions generate aneuploidies and micronuclei, which can undergo extensive chromosomal rearrangements such as chromothripsis1-5. (ox.ac.uk)
  • Selective pressures then shape distinct aneuploidy and rearrangement patterns-for example, in cancer6,7-but it is unknown whether initial biases in segregation errors and micronucleation exist for particular chromosomes. (ox.ac.uk)
  • We find that segregation error frequencies of individual chromosomes correlate with their location in the interphase nucleus, and show that this is highest for peripheral chromosomes behind spindle poles. (ox.ac.uk)
  • Our findings reveal a direct link between nuclear chromosome positions, segregation error frequencies and micronucleus content, with implications for our understanding of tumour genome evolution and the origins of specific aneuploidies during development. (ox.ac.uk)
  • Inhibition of transcription or RNA splicing phenocopies the chromosome alignment errors and spindle defects, suggesting that pericentric transcription during oocyte meiosis is required to regulate heterochromatin structure, chromosome segregation and maintenance of spindle organization. (bvsalud.org)
  • Cytotoxicity, cytostasis and genotoxicity were evaluated by the colorimetric assay of formazan reduction [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)] and by the cytokinesis-block micronucleus cytome (CBMN Cyt) assay. (birmingham.ac.uk)
  • Testing chemical agents with the cytokinesis-block micronucleus cytome assay. (sciensano.be)
  • Depletion of satellite RNA induces mesoscale changes in pericentric heterochromatin structure leading to chromosome instability, kinetochore attachment errors and abnormal chromosome alignment. (bvsalud.org)
  • Chromosome misalignment is associated with spindle defects, microtubule instability and, unexpectedly, loss of acentriolar microtubule organizing centre (aMTOC) tethering to spindle poles. (bvsalud.org)
  • Fluorescence in situ hybridization was conducted in combination with a bone marrow micronucleus test for measuring chromosomal instability. (bvsalud.org)
  • Chromosomal instability (CIN) induces a high rate of losses or gains of whole chromosomes or parts of chromosomes. (bvsalud.org)
  • To assess global chromosomal instability with high precision, we focused on the total number of DNA breakpoints of gains or losses of chromosome arms. (bvsalud.org)
  • Immunofluorescence, chromosome and micronuclei enumeration, MTT and colony formation assays were used to determine the effects of AP4 inactivation and target gene regulation on chromosomal instability (CIN) and drug sensitivity. (biomedcentral.com)
  • The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease described in about 50 patients worldwide and characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9. (biomedcentral.com)
  • Note that the instability is not in the centromere itself, but rather in the region adjacent to the centromere (qh), predominantly in chromosomes 1 and 16. (biomedcentral.com)
  • The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. (lookformedical.com)
  • A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. (lookformedical.com)
  • An aberration in which an extra chromosome or a chromosomal segment is made. (harvard.edu)
  • Overall, saxagliptin, the non-mutagenic antidiabetic drug, maintains chromosomal integrity in diabetes and reduces micronuclei formation by restoring redox imbalance, further indicating its usefulness in diabetic patients. (bvsalud.org)
  • Patient's cells display chromosome rearrangements, micronuclei, sensitivity to DNA damage and defective homologous recombination. (wikipedia.org)
  • The stochastic inheritance of chromosome fragments by both newly formed daughter cells could in part contribute to the alternating DNA copy-number states that are characteristic of chromothripsis 2 . (nature.com)
  • Sequencing of daughter cell pairs derived from micronucleated mother cells demonstrated that complex rearrangements are indeed a common outcome of micronucleus formation. (nature.com)
  • The comet assay revealed a dose-dependent increase in primary DNA damage, and a significant increase in oxidative damage to DNA was also detectable, as well as increased frequency of micronuclei in binucleated cells, often in a dose-related manner. (birmingham.ac.uk)
  • A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. (lookformedical.com)
  • Isolation and sequencing of single micronuclei from these cells showed that mis-segregating chromosomes frequently also preferentially become entrapped in micronuclei. (ox.ac.uk)
  • In addition, multipolar spindles and misaligned chromosomes were observed in a significant proportion of cells treated with PGF 2α . (arizona.edu)
  • Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.com)
  • ICF (OMIM #24242860) is a rare autosomal recessive disease that involves agammaglobulinemia or hypoglobulinemia with B cells as well as DNA rearrangements targeted to the centromere-adjacent heterochromatic region (qh) of chromosomes 1 and/or 16 (and sometimes 9) in mitogen-stimulated lymphocytes. (biomedcentral.com)
  • Mechanistically, the CIP2A-TOPBP1 complex prematurely associates with DNA lesions within ruptured micronuclei during interphase, which poises pulverized chromosomes for clustering upon mitotic entry. (nature.com)
  • Erythrocyte micronucleus frequencies in wild fish from two riverine environments and in fish reproduced and reared under controlled conditions (control group) were compared, with the aim to evaluate the suitability of the MN test for the in situ detection of mutagens in freshwaters. (torvergata.it)
  • Diabetic mice had a much higher incidence of micronuclei formation, and a centromeric DNA probe was present inside the majority of the induced micronuclei, indicating that most of these were caused by chromosome nondisjunction. (bvsalud.org)
  • Conversely, diabetic mice treated with saxagliptin exhibited a significant decrease in micronuclei induction, which were centromeric-positive and centromeric-negative. (bvsalud.org)
  • Mitotic clustering facilitates the reassembly of acentric fragments into rearranged chromosomes lacking the extensive DNA copy-number losses that are characteristic of canonical chromothripsis. (nature.com)
  • Thus, distinct patterns of chromothripsis can be explained by the spatial clustering of pulverized chromosomes from micronuclei. (nature.com)
  • Accordingly, chromothripsis in cancer genomes9 and aneuploidies in early development10 occur more frequently for larger chromosomes, which are preferentially located near the nuclear periphery. (ox.ac.uk)
  • However, most fragments derived from pulverized chromosomes are acentric and cannot directly bind to spindle microtubules 14 . (nature.com)
  • In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1). (lookformedical.com)
  • These studies implicate a potential mechanism suppressing the loss of genetic material after chromosome pulverization, although how distinct patterns of rearrangements arise in cancer and germline disorders remains unclear. (nature.com)
  • The frequency of these rearrangements is high enough to be detected upon routine cytogenetic examination of metaphase chromosomes. (biomedcentral.com)
  • Recent studies have revealed that variants of histone H2A and histone H3 play important roles not only in gene expression but also in the repair of DNA breaks and the assembly of chromosome centromeres. (sdbonline.org)
  • They found the genetic variants on chromosomes 2, 8, and 10 were significantly more common among Hodgkin lymphoma sufferers than healthy controls, and then confirmed the results in a further 2,057 cases and 3,416 controls. (regenerativemedicine.net)
  • The other genetic variants identified are also located in or near genes thought to play an important role in the immune system: REL on chromosome 2, GATA3 on chromosome 10, and PVT1 on chromosome 8. (regenerativemedicine.net)
  • Randomization of chromosome positions, Cas9-mediated live tracking and forced repositioning of individual chromosomes showed that a greater distance from the nuclear centre directly increases the propensity to mis-segregate. (ox.ac.uk)
  • Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. (sdbonline.org)
  • Much of this DNA hypomethylation is in 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. (biomedcentral.com)
  • Chromosome Duplication" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • A significantly higher frequency of micronuclei was observed in fish caught in the polluted river (Tibet), in comparison to both the controls and the Mignone river fish. (torvergata.it)
  • Barbels examined 50 and 100 days after capture presented a remarkable decrease in micronucleus frequency in comparison with the frequency observed in barbels at capture. (torvergata.it)
  • Importantly, the changes to the DNA regions on chromosomes 2, 6, and 8 were significantly more common in patients who had not been exposed to Epstein-Barr virus, implying that genes in these regions are involved in another way of triggering disease independently of the virus. (regenerativemedicine.net)
  • The micronucleus test in fish erythrocytes was shown to be a sensitive bioassay for detecting mutagenic pollution in fresh water environments. (torvergata.it)
  • For instance, defective lipid trafficking in the lack of NPC1 network marketing leads towards the lysosomal storage space disorder Niemann-Pick disease (Platt et al. (cancercurehere.com)
  • In yeast, SMC5/6 complex has sub-units which consists of SMC5, SMC6 and six nonstructural maintenance of chromosomes (NSE) proteins. (wikipedia.org)
  • Expression of dominant negative Rho attenuated the cell cycle delay and prevented the generation of micronuclei following treatment with PGF 2α . (arizona.edu)
  • The Human-Specific BOLA2 Duplication Modifies Iron Homeostasis and Anemia Predisposition in Chromosome 16p11.2 Autism Individuals. (harvard.edu)
  • In the worm Caenorhabditis elegans this complex interacts with the HIM-6(BLM) helicase to promote meiotic recombination intermediate processing and chromosome maturation. (wikipedia.org)