Dissertation/Thesis Abstract

Meiotic DSB repair and crossover control in NBS1 mutants of coprinus cinereus
by Crown, K. Nicole, Ph.D., Indiana University, 2011, 153; 3488049
Abstract (Summary)

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.

Indexing (document details)
Advisor: Zolan, Miriam
Commitee: Drummond, Jim, Ellison, Viola, Lacefield, Soni
School: Indiana University
Department: Biology
School Location: United States -- Indiana
Source: DAI-B 73/04, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Molecular biology, Genetics, Cellular biology
Keywords: Coprinopsis cinerea, Crossover control, Dna repair, Meiosis, Mrn complex, Nbs1 mutants
Publication Number: 3488049
ISBN: 9781267078131