One of the least understood aspects of homologous recombination is the process by which the ends of a double-strand break (DSB) search the entire genome for homologous templates that can be used to repair the break. We took advantage of the natural competition between the alternative donors HML and HMR employed during HO endonuclease-induced switching of the budding yeast MAT locus. The strong mating-type-dependent bias in the choice of the donors is enforced by the recombination enhancer (RE), which lies 17 kb proximal to HML . We investigated factors that improve the use of the disfavored donor. We show that the normal heterochromatic state of the donors does not impair donor usage, as donor choice is not affected by removing this epigenetic silencing. In contrast, increasing the length of homology shared by the disfavored donor increases its use. This result shows that donor choice is not irrevocable and implies that there are several encounters between the DSB ends and even the favored donor before recombination is accomplished. The increase by adding more homology is not linear; these results can be explained by a thermodynamic model that determines the energy cost of using one donor over the other. An important inference from this analysis is that when HML is favored as the donor, RE causes a reduction in its effective genomic distance from MAT from 200 kb to ∼20 kb, which we hypothesize occurs after the DSB is created, by epigenetic chromatin modifications around MAT . Received July 14, 2011. Accepted September 9, 2011. Copyright © 2011 by the Genetics Society of America Related articles Issue Highlights : ISSUE HIGHLIGHTS Genetics December 2011 189 : NP Full Text Full Text (PDF) « Previous | Next Article » Table of Contents This Article Published online before print September 27, 2011 , doi: 10.1534/genetics.111.132738 Genetics December 1, 2011 vol. 189 no. 4 1225-1233 » Abstract Full Text Full Text (PDF) Classifications Investigations Genome Integrity and Transmission Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Coïc, E. PubMed PubMed citation Articles by Coïc, E. Related Content Related articles in this journal Load related web page information This Months's Issue January 2012, 190 (1) Alert me to new issues of Genetics ABOUT SUBSCRIBE INFO FOR AUTHORS ONLINE SUBMISSION EDITORIAL BOARD CONTACT ALERTS HELP ADVERTISING RSS Help Contact Us International Access Link Print ISSN: 0016-6731 Online ISSN: 1943-2631 Copyright © 2012 by the Genetics Society of America phone: 412-268-1812 fax: 412-268-1813 email: genetics-gsa@andrew.cmu.edu
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