XB-ART-57056
Biology (Basel)
2017 Feb 08;61:. doi: 10.3390/biology6010012.
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The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis.
Potapova T
,
Gorbsky GJ
.
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Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.
???displayArticle.pubmedLink??? 28208750
???displayArticle.pmcLink??? PMC5372005
???displayArticle.link??? Biology (Basel)
???displayArticle.grants??? [+]
R01 GM111731 NIGMS NIH HHS
Genes referenced: kidins220 sgo2 tp53
GO keywords: chromosome segregation
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Figure 1. Mitotic defects have several potential outcomes. Failed alignment of chromosomes leads to mitotic arrest/delay enforced by the spindle checkpoint. If the failed alignment is not corrected, cells can follow several fates. They can undergo cell death directly from mitotic arrest. Cells may also suffer various kinds of abnormalities during mitotic exit, leading to the formation of aneuploid progeny. Alternatively, cells may exit mitosis without proper chromosome segregation and cytokinesis, resulting in a formation of a single tetraploid cell. Aneuploid or polyploid daughter cells may undergo cell death, cessation of proliferation and senescence, or continued proliferation. In most cases continued proliferation requires suppression or inactivation of the p53 tumor suppressor pathway. |
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Figure 2. Aneuploidy produces changes in mRNA dosage which lead to changes in protein dosage for genes on the gained or lost chromosome(s). Changed protein levels can have direct effects on biological processes in which they are involved, or change the stoichiometry of protein complexes of which they are components, causing changes in their function. Changes in gene dosage of regulatory proteins like transcription factors may also exert indirect effects on biological processes by altering expression of their target genes on other chromosomes. In most cases, alterations in protein levels are disadvantageous or detrimental for organisms adapted to their ordinary environment (left), where the euploid karyotype provides best fitness. However, under conditions of environmental change, rapid alterations in expression of many genes may provide adaptive potential and be selected (right). |
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Figure 3. Cell lines derived from cancers exhibit numerical and segmental aneuploidy. Spectral karyotype comparison of normal human mammary epithelial cells (HMEC) and two breast cancer cell lines (MCF-7 and SUM149PT) that exhibit extensive numerical and segmental aneuploidy. Image reproduced from [106]. |
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Figure 4. Numerical and segmental aneuploidy as an outcome of cohesion fatigue and centromere fission. A cell at metaphase will normally undergo balanced chromosome segregation in normal anaphase (upper path). If metaphase is delayed (lower path), chromatids may begin to undergo cohesion fatigue and separate. When sister chromatids separate they may both move to one of the two spindle poles leading to numerical aneuploidy following anaphase and mitotic exit. In other cases the kinetochore of an individual chromatid may undergo merotelic attachment to microtubules from both spindle poles (exemplified by sequential stages for the pink chromatid and detailed in the green boxes). Under this circumstance, spindle forces or cytokinesis may sever the chromatid resulting in chromosome fragments that can attach to other chromosomes resulting in segmental deletions, duplications, translocations and the formation of micronuclei. |
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Figure 5. Micronuclei present in two daughter LLC-Pk cells, a cell line derived from porcine kidney. Micronuclei likely formed from lagging chromosomes that were partially trapped in the cytokinetic cleavage furrow. The midbody, the remnant of the cleavage furrow, bisects the region between the two micronuclei. (micrographs courtesy of Hem Sapkota.) |
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Figure 6. Meiotic errors lead to aneuploid gametes. (A) Normal meiosis consists of two chromosome segregation events without an intervening S phase. In Meiosis I, homologous chromosomes pair and undergo recombination, forming crossovers. In anaphase of Meiosis I, the homologous chromosomes segregate. In Meiosis II sister chromatids separate. The final product is four haploid (1N) cells; (B) Defects in meiosis result in aneuploidy. In the example shown, the chromatids of one chromosome separate prematurely and segregate to opposite poles resulting in an imbalance of chromatids in the two cells produced by Meiosis I. When these cells undergo Meiosis II, each produces one normal haploid (1N) gamete and one aneuploid (1N + 1 or 1N − 1) gamete. For simplicity, only two chromosome pairs are depicted. |
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Figure 7. Loss of cohesin and the cohesin protector, Sgo2, in older mammals may lead to increased premature chromatid separation in meiosis. In young mammals (left) paired homologous chromosomes have high levels of cohesin and Sgo2 in Meiosis I (MI). At anaphase of Meiosis I, the protease, Separase, clips Cohesin on the distal chromosome arms allowing the homologous chromosomes to separate. Sgo2 protects Cohesin near the centromeres until Meiosis II (MII) ensuring that sister chromatids will orient to opposite poles. In aged mammals (right) there are diminished amounts of Cohesin and Sgo2. During Meiosis 1 Separase cleaves the majority of cohesin, including that near the centromeres. This allows sister chromatids to separate during anaphase of Meiosis I. In Meiosis II the individual chromatids may separate randomly to the spindle poles leading to a high incidence of aneuploidy. (Adapted from [163].) |
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Figure 8. Failed cytokinesis can lead to multipolar spindle formation in the subsequent mitosis. (A) A field of control HeLa cells containing mitotic cells showing normal chromosome alignment at metaphase (arrows); (B) HeLa cells were treated for a short time with an actin polymerization inhibitor drug, which blocks cytokinesis and results in the formation of binucleate polyploid cells containing extra centrosomes. During the subsequent mitosis, polyploid cells form abnormal metaphase chromosome alignments (arrows) when the presence of extra centrosomes leads to assembly of multipolar mitotic spindles. When these cells then undergo anaphase and cytokinesis, chromosomes are segregated in a random, unequal manner, leading to the formation of daughter cells that are highly aneuploid. Chromosomes are depicted in green; cell surfaces are depicted in magenta. |
References [+] :
Abramowitz,
Chromosome imbalance as a driver of sex disparity in disease.
2014, Pubmed
Abramowitz, Chromosome imbalance as a driver of sex disparity in disease. 2014, Pubmed
Andreassen, Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. 2001, Pubmed
Aylon, p53: guardian of ploidy. 2011, Pubmed
Baker, Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. 2013, Pubmed
Baker, BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. 2004, Pubmed
Balsas, Bortezomib resistance in a myeloma cell line is associated to PSMβ5 overexpression and polyploidy. 2012, Pubmed
Barnhart, Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis. 2011, Pubmed
Bekier, Length of mitotic arrest induced by microtubule-stabilizing drugs determines cell death after mitotic exit. 2009, Pubmed
Ben-David, Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells. 2014, Pubmed
Bergström, A high-definition view of functional genetic variation from natural yeast genomes. 2014, Pubmed
Beroukhim, The landscape of somatic copy-number alteration across human cancers. 2010, Pubmed
Bignell, Signatures of mutation and selection in the cancer genome. 2010, Pubmed
Birkbak, Paradoxical relationship between chromosomal instability and survival outcome in cancer. 2011, Pubmed
Bittles, The four ages of Down syndrome. 2007, Pubmed
Blasco, Telomeres and human disease: ageing, cancer and beyond. 2005, Pubmed
Bodnar, Extension of life-span by introduction of telomerase into normal human cells. 1998, Pubmed
Bomblies, The challenge of evolving stable polyploidy: could an increase in "crossover interference distance" play a central role? 2016, Pubmed
Bompard, P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring. 2013, Pubmed
Borneman, Whole-genome comparison reveals novel genetic elements that characterize the genome of industrial strains of Saccharomyces cerevisiae. 2011, Pubmed
Brinkley, Movement and segregation of kinetochores experimentally detached from mammalian chromosomes. 1988, Pubmed
Brito, Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. 2006, Pubmed
Brown, Awakening guardian angels: drugging the p53 pathway. 2009, Pubmed
Brunet, Functionality of the spindle checkpoint during the first meiotic division of mammalian oocytes. 2003, Pubmed
Carter, Absolute quantification of somatic DNA alterations in human cancer. 2012, Pubmed
Carter, A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. 2006, Pubmed
Casenghi, p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells. 1999, Pubmed
Castillo, Overexpression of Eg5 causes genomic instability and tumor formation in mice. 2007, Pubmed
Caulin, Peto's Paradox: evolution's prescription for cancer prevention. 2011, Pubmed
Chen, Targeting the adaptability of heterogeneous aneuploids. 2015, Pubmed
Chen, Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. 2012, Pubmed
Chiang, Age-dependent susceptibility of chromosome cohesion to premature separase activation in mouse oocytes. 2011, Pubmed
Chu, Cdk1/cyclin B plays a key role in mitotic arrest-induced apoptosis by phosphorylation of Mcl-1, promoting its degradation and freeing Bak from sequestration. 2012, Pubmed
Cimini, Anaphase spindle mechanics prevent mis-segregation of merotelically oriented chromosomes. 2004, Pubmed
Cimini, Merotelic kinetochore orientation is a major mechanism of aneuploidy in mitotic mammalian tissue cells. 2001, Pubmed
Crasta, DNA breaks and chromosome pulverization from errors in mitosis. 2012, Pubmed
Crockford, Cyclin D mediates tolerance of genome-doubling in cancers with functional p53. 2017, Pubmed
Dai, Slippage of mitotic arrest and enhanced tumor development in mice with BubR1 haploinsufficiency. 2004, Pubmed
Dalton, Human cancer cells commonly acquire DNA damage during mitotic arrest. 2007, Pubmed
Daum, Ska3 is required for spindle checkpoint silencing and the maintenance of chromosome cohesion in mitosis. 2009, Pubmed
Daum, Cohesion fatigue induces chromatid separation in cells delayed at metaphase. 2011, Pubmed , Xenbase
Davoli, Cumulative haploinsufficiency and triplosensitivity drive aneuploidy patterns and shape the cancer genome. 2013, Pubmed
Davoli, Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. 2012, Pubmed
Dephoure, Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast. 2014, Pubmed
Dewhurst, Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution. 2014, Pubmed
Di Nicolantonio, Replacement of normal with mutant alleles in the genome of normal human cells unveils mutation-specific drug responses. 2008, Pubmed
Duelli, Cell-to-cell fusion as a link between viruses and cancer. 2007, Pubmed
Duensing, Guilt by association? p53 and the development of aneuploidy in cancer. 2005, Pubmed
Duesberg, Origin of multidrug resistance in cells with and without multidrug resistance genes: chromosome reassortments catalyzed by aneuploidy. 2001, Pubmed
Duesberg, Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy. 2000, Pubmed
Duesberg, How aneuploidy may cause cancer and genetic instability. 1999, Pubmed
Duncan, Frequent aneuploidy among normal human hepatocytes. 2012, Pubmed
Duncan, Chromosome cohesion decreases in human eggs with advanced maternal age. 2012, Pubmed
Dunham, Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. 2002, Pubmed
Dunn, Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments. 2012, Pubmed
Eaker, Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice. 2001, Pubmed
Eggert, Animal cytokinesis: from parts list to mechanisms. 2006, Pubmed
Faggioli, Cell fusion is a physiological process in mouse liver. 2008, Pubmed
Fragouli, The cytogenetics of polar bodies: insights into female meiosis and the diagnosis of aneuploidy. 2011, Pubmed
Frias, Telomere dysfunction and genome instability. 2012, Pubmed
Fries, Serial isolates of Cryptococcus neoformans from patients with AIDS differ in virulence for mice. 1998, Pubmed
Fritz, Cytogenetic analyses of culture failures by comparative genomic hybridisation (CGH)-Re-evaluation of chromosome aberration rates in early spontaneous abortions. 2001, Pubmed
Fujiwara, Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. 2005, Pubmed
Galimberti, Anaphase catastrophe is a target for cancer therapy. 2011, Pubmed
Galipeau, 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett's esophagus. 1996, Pubmed
Gallardo, Discovery of tetraploidy in a mammal. 1999, Pubmed
Gallone, Domestication and Divergence of Saccharomyces cerevisiae Beer Yeasts. 2016, Pubmed
Ganem, Tetraploidy, aneuploidy and cancer. 2007, Pubmed
Ganem, Cytokinesis failure triggers hippo tumor suppressor pathway activation. 2014, Pubmed
Ganem, A mechanism linking extra centrosomes to chromosomal instability. 2009, Pubmed
Gascoigne, Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. 2008, Pubmed
Geigl, Defining 'chromosomal instability'. 2008, Pubmed
Gerlinger, Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. 2012, Pubmed
Gerstein, Shift and adapt: the costs and benefits of karyotype variations. 2015, Pubmed
Gerstein, Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation. 2015, Pubmed
Giam, Aneuploidy and chromosomal instability in cancer: a jackpot to chaos. 2015, Pubmed
Giannoudis, Basal keratinocyte tetrasomy in low-grade squamous intra-epithelial lesions of the cervix is restricted to high and intermediate risk HPV infection but is not type-specific. 2000, Pubmed
Giménez-Abián, Regulation of sister chromatid cohesion between chromosome arms. 2004, Pubmed
Gisselsson, Abnormal nuclear shape in solid tumors reflects mitotic instability. 2001, Pubmed
Gisselsson, Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis. 2010, Pubmed
Glotzer, The molecular requirements for cytokinesis. 2005, Pubmed
Godinho, Centrosomes and cancer: how cancer cells divide with too many centrosomes. 2009, Pubmed
Golomb, p53 and ribosome biogenesis stress: the essentials. 2014, Pubmed
Gorbsky, The mitotic spindle checkpoint. 2001, Pubmed
Gordon, Causes and consequences of aneuploidy in cancer. 2012, Pubmed
Gresham, The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. 2008, Pubmed
Guerrero, Centromere-localized breaks indicate the generation of DNA damage by the mitotic spindle. 2010, Pubmed
Guo, Drug Resistance in Colorectal Cancer Cell Lines is Partially Associated with Aneuploidy Status in Light of Profiling Gene Expression. 2016, Pubmed
Hama, Molecular lesions in childhood and adult acute megakaryoblastic leukaemia. 2012, Pubmed
Hanahan, Hallmarks of cancer: the next generation. 2011, Pubmed
Hanks, Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. 2004, Pubmed
Harley, Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. 2010, Pubmed
Harrison, A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole. 2014, Pubmed
Hartman, Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. 2007, Pubmed
Hatch, Catastrophic nuclear envelope collapse in cancer cell micronuclei. 2013, Pubmed
Hayashi, A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. 2012, Pubmed
Hellsten, Accelerated gene evolution and subfunctionalization in the pseudotetraploid frog Xenopus laevis. 2007, Pubmed , Xenbase
Heng, Evolutionary mechanisms and diversity in cancer. 2011, Pubmed
Hinchcliffe, Chromosome missegregation during anaphase triggers p53 cell cycle arrest through histone H3.3 Ser31 phosphorylation. 2016, Pubmed
Hirano, Virally transformed cells and cytochalasin B. I. The effect of cytochalasin B on cytokinesis, karyokinesis and DNA synthesis in cells. 1974, Pubmed
Hoffelder, Resolution of anaphase bridges in cancer cells. 2004, Pubmed
Hoffmann, A single bivalent efficiently inhibits cyclin B1 degradation and polar body extrusion in mouse oocytes indicating robust SAC during female meiosis I. 2011, Pubmed
Homer, Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes. 2005, Pubmed
Horn, Coping with stress: multiple ways to activate p53. 2007, Pubmed
How, Chromosomal instability as a prognostic marker in cervical cancer. 2015, Pubmed
Hu, Development and function of trophoblast giant cells in the rodent placenta. 2010, Pubmed
Hughes, Widespread aneuploidy revealed by DNA microarray expression profiling. 2000, Pubmed
Incassati, Induction of tetraploidy through loss of p53 and upregulation of Plk1 by human papillomavirus type-16 E6. 2006, Pubmed
Iwanaga, Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice. 2007, Pubmed
Jacquemont, High risk of malignancy in mosaic variegated aneuploidy syndrome. 2002, Pubmed
Janssen, Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. 2011, Pubmed
Jeganathan, Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. 2007, Pubmed
Jordan, Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. 1993, Pubmed
Kaufman, New insights into triploidy and tetraploidy, from an analysis of model systems for these conditions. 1991, Pubmed
Khan, Myeloid leukemia in Down syndrome. 2011, Pubmed
Khan, p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest. 1998, Pubmed
Komlodi-Pasztor, Mitosis is not a key target of microtubule agents in patient tumors. 2011, Pubmed
Korthout, A tormentor in the quest for plant p53-like proteins. 2002, Pubmed
Krzywicka-Racka, Repeated cleavage failure does not establish centrosome amplification in untransformed human cells. 2011, Pubmed
Kuliev, Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. 2011, Pubmed
Kuznetsova, Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. 2015, Pubmed
Kvitek, Variations in stress sensitivity and genomic expression in diverse S. cerevisiae isolates. 2008, Pubmed
Kwon, Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. 2008, Pubmed
Lambrus, p53 protects against genome instability following centriole duplication failure. 2015, Pubmed
Lanni, Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. 1998, Pubmed
Lara-Gonzalez, Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a spindle checkpoint-dependent mitotic arrest. 2012, Pubmed
LeMaire-Adkins, Lack of checkpoint control at the metaphase/anaphase transition: a mechanism of meiotic nondisjunction in mammalian females. 1997, Pubmed
Leber, Proteins required for centrosome clustering in cancer cells. 2010, Pubmed
Lee, Endoreplication: polyploidy with purpose. 2009, Pubmed
Lee, Chromosomal instability confers intrinsic multidrug resistance. 2011, Pubmed
Lee, Mechanisms and Consequences of Cancer Genome Instability: Lessons from Genome Sequencing Studies. 2016, Pubmed
Leibowitz, Chromothripsis: A New Mechanism for Rapid Karyotype Evolution. 2015, Pubmed
Lengauer, Genetic instabilities in human cancers. 1998, Pubmed
Lentini, Simultaneous reduction of MAD2 and BUBR1 expression induces mitotic spindle alterations associated with p53 dependent cell cycle arrest and death. 2014, Pubmed
Leroi, Cancer selection. 2003, Pubmed
Lister, Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. 2010, Pubmed
Liu, Defective cohesin is associated with age-dependent misaligned chromosomes in oocytes. 2008, Pubmed
Ljunger, Chromosomal anomalies in first-trimester miscarriages. 2005, Pubmed
Lopes, Transcriptional changes in response to X chromosome dosage in the mouse: implications for X inactivation and the molecular basis of Turner Syndrome. 2010, Pubmed
Luzhna, Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond. 2013, Pubmed
Ly, Characterization of aneuploid populations with trisomy 7 and 20 derived from diploid human colonic epithelial cells. 2011, Pubmed
Ly, Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining. 2017, Pubmed
Maciejowski, Chromothripsis and Kataegis Induced by Telomere Crisis. 2015, Pubmed
Manning, Whole chromosome instability resulting from the synergistic effects of pRB and p53 inactivation. 2014, Pubmed
Manning, Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion. 2014, Pubmed
Manning, Loss of pRB causes centromere dysfunction and chromosomal instability. 2010, Pubmed
Martínez-A, Centromere fission, not telomere erosion, triggers chromosomal instability in human carcinomas. 2011, Pubmed
Matsumoto, Aging-associated vascular phenotype in mutant mice with low levels of BubR1. 2007, Pubmed
Matsuura, Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. 2006, Pubmed
Michel, MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. 2001, Pubmed
Minshull, A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extracts. 1994, Pubmed , Xenbase
Mitchison, The proliferation rate paradox in antimitotic chemotherapy. 2012, Pubmed
Morales, Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities. 2008, Pubmed
Mullins, Terminal phase of cytokinesis in D-98s cells. 1977, Pubmed
Murray, Cyclin synthesis drives the early embryonic cell cycle. 1989, Pubmed , Xenbase
Na, Aneuploidy in pluripotent stem cells and implications for cancerous transformation. 2014, Pubmed
Nagaoka, Human aneuploidy: mechanisms and new insights into an age-old problem. 2012, Pubmed
Nagata, Thrombopoietin-induced polyploidization of bone marrow megakaryocytes is due to a unique regulatory mechanism in late mitosis. 1997, Pubmed
Nakamura, A tetraploid liveborn neonate: cytogenetic and autopsy findings. 2003, Pubmed
Navin, Cancer genomics: one cell at a time. 2014, Pubmed
Navin, Inferring tumor progression from genomic heterogeneity. 2010, Pubmed
Navin, Tumour evolution inferred by single-cell sequencing. 2011, Pubmed
Navin, The first five years of single-cell cancer genomics and beyond. 2015, Pubmed
Nguyen, Dosage compensation of the active X chromosome in mammals. 2006, Pubmed
Nicholson, Chromosome mis-segregation and cytokinesis failure in trisomic human cells. 2015, Pubmed
Nigg, Origins and consequences of centrosome aberrations in human cancers. 2006, Pubmed
North, SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. 2014, Pubmed
O'Connell, The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes. 2008, Pubmed
Okagaki, Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections. 2012, Pubmed
Okamura, Generation of hybrid hepatocytes by cell fusion from monkey embryoid body cells in the injured mouse liver. 2006, Pubmed
Olaharski, Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. 2006, Pubmed
Olivier, TP53 mutations in human cancers: origins, consequences, and clinical use. 2010, Pubmed
Opyrchal, Inhibition of Cdk2 kinase activity selectively targets the CD44⁺/CD24⁻/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells. 2014, Pubmed
Ornitz, Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. 1987, Pubmed
Orth, Prolonged mitotic arrest triggers partial activation of apoptosis, resulting in DNA damage and p53 induction. 2012, Pubmed
Otter, Triple X syndrome: a review of the literature. 2010, Pubmed
Otto, The evolutionary consequences of polyploidy. 2007, Pubmed
Ottolini, Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. 2015, Pubmed
Pan, Age-associated increase in aneuploidy and changes in gene expression in mouse eggs. 2008, Pubmed
Passerini, The presence of extra chromosomes leads to genomic instability. 2016, Pubmed
Pavelka, Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. 2010, Pubmed
Pavelka, Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer. 2010, Pubmed
Pawelek, Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. 2008, Pubmed
Peto, Quantitative implications of the approximate irrelevance of mammalian body size and lifespan to lifelong cancer risk. 2015, Pubmed
Potapova, Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. 2016, Pubmed
Potapova, The reversibility of mitotic exit in vertebrate cells. 2006, Pubmed , Xenbase
Potapova, Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos. 2013, Pubmed
Puig, Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy. 2008, Pubmed
Quintyne, Spindle multipolarity is prevented by centrosomal clustering. 2005, Pubmed
Rainis, The proto-oncogene ERG in megakaryoblastic leukemias. 2005, Pubmed
Rancati, Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. 2008, Pubmed
Rankin, Recent advances in cohesin biology. 2016, Pubmed
Rehen, Constitutional aneuploidy in the normal human brain. 2005, Pubmed
Renny-Byfield, Doubling down on genomes: polyploidy and crop plants. 2014, Pubmed
Revenkova, Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy. 2010, Pubmed
Ricke, Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation. 2011, Pubmed
Roberts, Unique mosaicism of tetraploidy and trisomy 8: clinical, cytogenetic, and molecular findings in a live-born infant. 1996, Pubmed
Rutledge, Selective advantage of trisomic human cells cultured in non-standard conditions. 2016, Pubmed
Sakurikar, Cyclin-dependent kinase-1 (Cdk1)/cyclin B1 dictates cell fate after mitotic arrest via phosphoregulation of antiapoptotic Bcl-2 proteins. 2012, Pubmed
Salman-Minkov, Whole-genome duplication as a key factor in crop domestication. 2016, Pubmed
Sansam, Connecting by breaking and repairing: mechanisms of DNA strand exchange in meiotic recombination. 2015, Pubmed
Santaguida, Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. 2010, Pubmed
Schiff, Taxol stabilizes microtubules in mouse fibroblast cells. 1980, Pubmed
Schiff, Promotion of microtubule assembly in vitro by taxol. 1979, Pubmed
Schmidt, Ablation of the spindle assembly checkpoint by a compound targeting Mps1. 2005, Pubmed
Schvartzman, Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition. 2011, Pubmed
Scott, Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour. 2006, Pubmed
Selmecki, An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. 2008, Pubmed
Selmecki, Aneuploidy and isochromosome formation in drug-resistant Candida albicans. 2006, Pubmed
Selmecki, Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance. 2009, Pubmed
Session, Genome evolution in the allotetraploid frog Xenopus laevis. 2016, Pubmed , Xenbase
Shah, The clonal and mutational evolution spectrum of primary triple-negative breast cancers. 2012, Pubmed
Shao, Xenopus oocyte meiosis lacks spindle assembly checkpoint control. 2013, Pubmed , Xenbase
Sharma, Small-molecule inhibitor BMS-777607 induces breast cancer cell polyploidy with increased resistance to cytotoxic chemotherapy agents. 2013, Pubmed
Sheltzer, Aneuploidy drives genomic instability in yeast. 2011, Pubmed
Siegel, New insights into the troubles of aneuploidy. 2012, Pubmed
Silk, Chromosome missegregation rate predicts whether aneuploidy will promote or suppress tumors. 2013, Pubmed
Sloss, Mcl-1 dynamics influence mitotic slippage and death in mitosis. 2016, Pubmed
Soltis, Polyploidy and genome evolution in plants. 2015, Pubmed
Sotillo, Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. 2007, Pubmed
Stankiewicz, ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. 2009, Pubmed
Stefanova, Mosaic and complete tetraploidy in live-born infants: two new patients and review of the literature. 2010, Pubmed
Steigemann, Aurora B-mediated abscission checkpoint protects against tetraploidization. 2009, Pubmed
Stephens, Massive genomic rearrangement acquired in a single catastrophic event during cancer development. 2011, Pubmed
Steuerwald, Maternal age-related differential global expression profiles observed in human oocytes. 2007, Pubmed
Stevens, Uncoordinated loss of chromatid cohesion is a common outcome of extended metaphase arrest. 2011, Pubmed
Stingele, Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells. 2012, Pubmed
Storchová, Genome-wide genetic analysis of polyploidy in yeast. 2006, Pubmed
Sulak, TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. 2016, Pubmed
Swanton, Chromosomal instability determines taxane response. 2009, Pubmed
Sybert, Turner's syndrome. 2004, Pubmed
Sánchez Alvarado, Cellular hyperproliferation and cancer as evolutionary variables. 2012, Pubmed
Tachibana-Konwalski, Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. 2010, Pubmed
Thompson, Chromosome missegregation in human cells arises through specific types of kinetochore-microtubule attachment errors. 2011, Pubmed
Thompson, Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. 2010, Pubmed
Thomson, High frame-rate resolution of cell division during Candida albicans filamentation. 2016, Pubmed
Torres, Identification of aneuploidy-tolerating mutations. 2010, Pubmed
Torres, Effects of aneuploidy on cellular physiology and cell division in haploid yeast. 2007, Pubmed
Tsutsumi, Age-related decrease of meiotic cohesins in human oocytes. 2014, Pubmed
Uetake, Prolonged prometaphase blocks daughter cell proliferation despite normal completion of mitosis. 2010, Pubmed
Upender, Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. 2004, Pubmed
Visootsak, Klinefelter syndrome and other sex chromosomal aneuploidies. 2006, Pubmed
Vitale, Multipolar mitosis of tetraploid cells: inhibition by p53 and dependency on Mos. 2010, Pubmed
Vitrat, Endomitosis of human megakaryocytes are due to abortive mitosis. 1998, Pubmed
Vogelstein, Surfing the p53 network. 2000, Pubmed
Voordeckers, Adaptation to High Ethanol Reveals Complex Evolutionary Pathways. 2015, Pubmed
Vousden, p53 in health and disease. 2007, Pubmed
Vrooman, Evidence for paternal age-related alterations in meiotic chromosome dynamics in the mouse. 2014, Pubmed
Wang, BUBR1 deficiency results in abnormal megakaryopoiesis. 2004, Pubmed
Wang, Clonal evolution in breast cancer revealed by single nucleus genome sequencing. 2014, Pubmed
Waters, Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. 1998, Pubmed
Weaver, Aneuploidy acts both oncogenically and as a tumor suppressor. 2007, Pubmed
Weinstein, The Cancer Genome Atlas Pan-Cancer analysis project. 2013, Pubmed
Werbowetski-Ogilvie, Characterization of human embryonic stem cells with features of neoplastic progression. 2009, Pubmed
Wheatley, Binucleation in mammalian liver. Studies on the control of cytokinesis in vivo. 1972, Pubmed
Williams, Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. 2008, Pubmed
Wong, Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. 2015, Pubmed
Yun, Reduced ability to recover from spindle disruption and loss of kinetochore spindle assembly checkpoint proteins in oocytes from aged mice. 2014, Pubmed
Yun, Premature dyad separation in meiosis II is the major segregation error with maternal age in mouse oocytes. 2014, Pubmed
Zack, Pan-cancer patterns of somatic copy number alteration. 2013, Pubmed
Zasadil, 2n or not 2n: Aneuploidy, polyploidy and chromosomal instability in primary and tumor cells. 2013, Pubmed
Zasadil, Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles. 2014, Pubmed
Zhang, Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential. 2016, Pubmed
Zhang, Overexpression of spindlin1 induces metaphase arrest and chromosomal instability. 2008, Pubmed
Zhang, Generation of cancer stem-like cells through the formation of polyploid giant cancer cells. 2014, Pubmed
Zhang, Chromothripsis from DNA damage in micronuclei. 2015, Pubmed
Zhimulev, Polytene chromosomes: 70 years of genetic research. 2004, Pubmed
Zhu, Karyotypic determinants of chromosome instability in aneuploid budding yeast. 2012, Pubmed
Zimonjic, Derivation of human tumor cells in vitro without widespread genomic instability. 2001, Pubmed
Zybina, Polytene chromosomes in mammalian cells. 1996, Pubmed
de Bruin, Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. 2014, Pubmed