It is well established that Nbs1, a member of the MRN complex (Mre11-Rad50-Nbs1), plays an essential role in the cellular response to DNA double-stranded breaks. While Nbs1 is also required for successful meiosis, its specific roles are not well characterized. I am using the basidiomycete Coprinus cinereus to examine the meiotic roles of Nbs1. The Forkhead-associated (FHA) domain of Nbs1 is involved in phospho-dependent protein-protein interactions and is responsible for locating the protein (and the rest of the MRN complex) to sites of DNA damage. I have shown that a strain with a mutation in this domain, nbs1-2, has a higher frequency of meiosis I nondisjunction, an altered crossover distribution, loss of crossover interference, and faster repair of meiotic DSBs. I propose a model in which there is a window of opportunity for a given DSB to be repaired as a crossover, and that in nbs1-2, faster repair of more DSBs during that window causes the loss of crossover control. This results in more double crossovers in nbs1-2, at least some of which have a smaller region of exchange between homologs. The double crossovers also disrupt the association of exchange regions with the nuclear envelope. These smaller regions of exchange cause unstable chiasma, leading to a higher frequency of meiosis I nondisjunction.
|Commitee:||Drummond, Jim, Ellison, Viola, Lacefield, Soni|
|School Location:||United States -- Indiana|
|Source:||DAI-B 73/04, Dissertation Abstracts International|
|Subjects:||Molecular biology, Genetics, Cellular biology|
|Keywords:||Coprinopsis cinerea, Crossover control, Dna repair, Meiosis, Mrn complex, Nbs1 mutants|
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