MLH1 and MSH2 promote the symmetry of double-strand break repair events at the HIS4 hotspot in Saccharomyces cerevisiae

Hoffmann, E. R., Eriksson, E., Herbert, B. J. and Borts, R. H. (2005) MLH1 and MSH2 promote the symmetry of double-strand break repair events at the HIS4 hotspot in Saccharomyces cerevisiae. Genetics, 169 (3). pp. 1291-303. ISSN 0016-6731

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Abstract

Double-strand breaks (DSBs) initiate meiotic recombination. The DSB repair model predicts that both genetic markers spanning the DSB should be included in heteroduplex DNA and be detectable as non-Mendelian segregations (NMS). In experiments testing this, a significant fraction of events do not conform to this prediction, as only one of the markers displays NMS (one-sided events). Two explanations have been proposed to account for the discrepancies between the predictions and experimental observations. One suggests that two-sided events are the norm but are "hidden" as heteroduplex repair frequently restores the parental configuration of one of the markers. Another explanation posits that one-sided events reflect events in which heteroduplex is formed predominantly on only one side of the DSB. In the absence of heteroduplex repair, the first model predicts that two-sided events would be revealed at the expense of one-sided events, while the second predicts no effect on the distribution of events when heteroduplex repair is lost. We tested these predictions by deleting the DNA mismatch repair genes MSH2 or MLH1 and analyzing the proportion of two-sided events. Unexpectedly, the results do not match the predictions of either model. In both mlh1Delta and msh2Delta, the proportion of two-sided events is significantly decreased relative to wild type. These observations can be explained in one of two ways. Either Msh2p/Mlh1p-independent mispair removal leads to restoration of one of the markers flanking the DSB site or Msh2p/Mlh1p actively promote two-sided events.

Item Type: Article
Additional Information: 0016-6731 (Print) Journal Article
Keywords: Alcohol Oxidoreductases/*metabolism Aminohydrolases/*metabolism *Base Pair Mismatch Base Sequence Chromosome Mapping Chromosomes, Fungal DNA Primers *DNA Repair DNA-Binding Proteins/*metabolism Fungal Proteins/*metabolism Models, Genetic Molecular Sequence Data MutS Homolog 2 Protein Polymerase Chain Reaction Pyrophosphatases/*metabolism Research Support, Non-U.S. Gov't Saccharomyces cerevisiae/*genetics Saccharomyces cerevisiae Proteins/*metabolism
Schools and Departments: School of Life Sciences
Depositing User: Gee Wheatley
Date Deposited: 19 Mar 2007
Last Modified: 30 Nov 2012 16:51
URI: http://sro.sussex.ac.uk/id/eprint/947
Google Scholar:15 Citations
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