Cell Type Regulates Selective Segregation of Mouse Chromosome 7 DNA Strands in Mitosis

Armakolas, Athanasios; Klar, Amar J. S.

doi:10.1126/science.1120519

Cited by 100 publications

(111 citation statements)

References 17 publications

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“…We suggest that strandspecific imprinting along with nonrandom segregation mechanisms may have evolved as one of the avenues to produce multiple arrays of cell types in higher eukaryotes (Klar 2004b). In mouse embryonic stem cells, the data indicates that parental chromosome 7 Watson strands always co-segregate to the same daughter cell leaving Crick strands to go to the sister cell (Armakolas and Klar 2006;Armakolas and Klar 2007). Such biased chromatid segregation is proposed to be a mechanism for development in higher organisms (Klar 2008;Armakolas et al 2010;Sauer and Klar 2012).…”

Section: Discussionmentioning

confidence: 91%

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

Klar

Bonaduce

2013

Chromosome Res

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The base complementarity feature (Watson and Crick in Nature 171(4356): [737][738] 1953) and the rule of semi-conservative mode of DNA replication (Messelson and Stahl in Proc Natl Acad Sci U S A 44: [671][672][673][674][675][676][677][678][679][680][681][682] 1958) dictate that two identical replicas of the parental chromosome are produced during replication. In principle, the inherent strand sequence differences could generate nonequivalent daughter chromosome replicas if one of the two strands were epigenetically imprinted during replication to effect silencing/expression of developmentally important genes. Indeed, inheritance of such a strand-and sitespecific imprint confers developmental asymmetry to fission yeast sister cells by a phenomenon called mating/cell-type switching. Curiously, location of DNA strands with respect to each other at the centromere is fixed, and as a result, their selected segregation to specific sister chromatid copies occurs in eukaryotic cells. The yeast system provides a unique opportunity to determine the significance of such biased strand distribution to sister chromatids. We determined whether the cylindrical-shaped yeast cell distributes the specific chromosomal strand to the same cellular pole in successive cycles of cell division. By observing the pattern of recurrent mating-type switching in progenies of individual cells by microscopic analyses, we found that chromosome 2 strands are distributed by the random mode in successive cell divisions. We also exploited unusual "hotspot" recombination features of this system to investigate whether there is selective segregation of strands such that oldest Watsoncontaining strands co-segregate in the diploid cell at mitosis. Our data suggests that chromosome 2 strands are segregated independently to those of the homologous chromosome.

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Section: Discussionmentioning

confidence: 91%

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

Klar

Bonaduce

2013

Chromosome Res

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“…Thus, different frequencies of LOH in particular cell types may be the consequence of the relative fraction of z segregation and may be related to the cell cycle compartment in which recombination occurs. Also, it could be related to variability of nonrandom segregation of original and newly replicated DNA strands [59] and may even vary between individual chromosome pairs within a specific single cell type. Thus, patterns of LOH might be directly related to organismal development and cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Homologous Recombination Conserves DNA Sequence Integrity Throughout the Cell Cycle in Embryonic Stem Cells

Serrano

Liang

Chang

et al. 2011

Stem Cells and Development

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“…One simple explanation is that the Trp53-/-epithelium contains less quiescent cells than wild type, which is possible considering the important role of p53 in regulation of cell cycle checkpoint and senescence. Another rather tempting explanation is that p53 may regulate the partition of sister chromatids during mitosis, which could be decisive for the fate of daughter cells 19 . We showed that p53 negatively regulated MaSCs self-renewal and that Trp53-/-epithelium contained more long-term regenerative MaSCs than wild type epithelium.…”

Section: Resultsmentioning

confidence: 99%

Regulation of Mammary Progenitor Cells by p53 and Parity

Tao¹,

Jerry²

2010

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE:01-01-2010 REPORT TYPE:Annual Summary Report DATES COVERED (From PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Massachusetts-Amherst PERFORMING ORGANIZATION REPORT NUMBERAmherst, Massachusetts, 01003 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S.Army Medical Research and Material CommandFort Detrick, Maryland, 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S)12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTBreast cancer is the most frequent cancer among women in the United States. A full term pregnancy early in reproductive life can reduce breast cancer incidence in women by up to 50% and p53, an important tumor suppressor gene, was shown to be a major effector for this protection effect. We hypothesized that p53 may negatively regulate the proliferation and self-renewal of mammary stem/progenitor cells and that the increased p53 in parous gland may limit mammary stem/progenitor cells population and reduce the transformation risk. Mammosphere assays showed that decreased p53 dosage in Trp53+/-and Trp53-/-mice led to increased numbers and size of mammospheres. Meanwhile, the number of secondary and tertiary mammospheres was not affected by (IR) regardless of their genotype. The cell cycle analysis also showed that the Trp53-/-mammospheres have higher proliferation rate than Trp53+/+ spheres. Serial dilution and transplantation experiments also showed that the Trp53-/-epithelium had significantly increased frequency of long-term regenerative MaSCs compared to Trp53+/+ epithelium. The BrdU labeling experiment showed that Trp53-/-mammary gland contains less label-retaining epithelial cells (LRECs) than Trp53+/+ epithelium. Our data suggest that p53 negatively regulates the self-renewal of mammary stem cells. The MaSCs pool expands with decreased p53 dosage, which may result in a higher transformation risk. Meanwhile, the p53-mediated apoptosis pathway is compromised in the mammosphere-initiating cells.

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Cell Type Regulates Selective Segregation of Mouse Chromosome 7 DNA Strands in Mitosis

Cited by 100 publications

References 17 publications

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

Unbiased segregation of fission yeast chromosome 2 strands to daughter cells

Homologous Recombination Conserves DNA Sequence Integrity Throughout the Cell Cycle in Embryonic Stem Cells

Regulation of Mammary Progenitor Cells by p53 and Parity

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