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The Conserved Pch2 Gene Acts To Regulate Dna Doublestrand Break Repair In Saccharomyces Cerevisiae Meiosis

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In the first chromosome division of meiosis (MI), homologous chromosome pairs are separated, allowing for the production of fertile haploid gametes from diploid progenitor cells. Proper MI segregation of homologous chromosomes in most eukaryotic organisms requires that at least one programmed DNA double-strand break (DSB) per pair of homologous chromosomes is repaired as a crossover. These crossover events tether homologous chromosomes together, which allows for the generation of a bipolar spindle to separate the homologous chromosomes. The widely conserved PCH2 gene of Saccharomyces cerevisiae is involved in regulating the repair of meiotic DSBs. First, Pch2 promotes the use of the homologous chromosome, instead of the sister chromatid, as a DSB repair template. Second, Pch2 regulates the fate of DSBs that are repaired using the homologous chromosome by limiting gene conversion and by promoting crossover interference. pch2 mutants repair a greater proportion of meiotic DSBs using the sister chromatid than wild-type cells, but the majority of DSBs are still repaired using the homologous chromosome. The DSBs that are repaired using the homologous chromosome in pch2 mutants have a higher likelihood to be associated with gene conversion events and to be repaired as crossovers, as opposed to noncrossovers. The distribution of crossover events observed in pch2 also demonstrates a significant reduction in crossover interference in these mutants. I hypothesize that a single Pch2-dependent role in meiotic chromosome axis organization inhibits intersister DSB repair, limits gene conversion tract length, and promotes the interference regulation of interhomolog DSB repair.

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2010-10-20

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dissertation or thesis

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