The Rad52-Y66A Allele Alters the Choice of Donor Template During Spontaneous Chromosomal Recombination

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2009 Nov 7

PMID 19892607

Citations 5

Authors

Adriana Antunez de Mayolo

Ivana Sunjevaric

Robert Reid

Uffe H Mortensen

Rodney Rothstein

Michael Lisby

Affiliations

Soon will be listed here.

Abstract

Spontaneous mitotic recombination is a potential source of genetic changes such as loss of heterozygosity and chromosome translocations, which may lead to genetic disease. In this study we have used a rad52 hyper-recombination mutant, rad52-Y66A, to investigate the process of spontaneous heteroallelic recombination in the yeast Saccharomyces cerevisiae. We find that spontaneous recombination has different genetic requirements, depending on whether the recombination event occurs between chromosomes or between chromosome and plasmid sequences. The hyper-recombination phenotype of the rad52-Y66A mutation is epistatic with deletion of MRE11, which is required for establishment of DNA damage-induced cohesion. Moreover, single-cell analysis of strains expressing YFP-tagged Rad52-Y66A reveals a close to wild-type frequency of focus formation, but with foci lasting 6 times longer. This result suggests that spontaneous DNA lesions that require recombinational repair occur at the same frequency in wild-type and rad52-Y66A cells, but that the recombination process is slow in rad52-Y66A cells. Taken together, we propose that the slow recombinational DNA repair in the rad52-Y66A mutant leads to a by-pass of the window-of-opportunity for sister chromatid recombination normally promoted by MRE11-dependent damage-induced cohesion thereby causing a shift towards interchromosomal recombination.

Citing Articles

Rad52 sumoylation prevents the toxicity of unproductive Rad51 filaments independently of the anti-recombinase Srs2.

Esta A, Ma E, Dupaigne P, Maloisel L, Guerois R, Le Cam E PLoS Genet. 2013; 9(10):e1003833.

PMID: 24130504 PMC: 3794917. DOI: 10.1371/journal.pgen.1003833.

Histone H3K56 acetylation, Rad52, and non-DNA repair factors control double-strand break repair choice with the sister chromatid.

Munoz-Galvan S, Jimeno S, Rothstein R, Aguilera A PLoS Genet. 2013; 9(1):e1003237.

PMID: 23357952 PMC: 3554610. DOI: 10.1371/journal.pgen.1003237.

RSC facilitates Rad59-dependent homologous recombination between sister chromatids by promoting cohesin loading at DNA double-strand breaks.

Oum J, Seong C, Kwon Y, Ji J, Sid A, Ramakrishnan S Mol Cell Biol. 2011; 31(19):3924-37.

PMID: 21807899 PMC: 3187356. DOI: 10.1128/MCB.01269-10.

Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis.

Goldfarb T, Lichten M PLoS Biol. 2010; 8(10):e1000520.

PMID: 20976044 PMC: 2957403. DOI: 10.1371/journal.pbio.1000520.

Enhancement of gene targeting in human cells by intranuclear permeation of the Saccharomyces cerevisiae Rad52 protein.

Kalvala A, Rainaldi G, Di Primio C, Liverani V, Falaschi A, Galli A Nucleic Acids Res. 2010; 38(14):e149.

PMID: 20519199 PMC: 2919737. DOI: 10.1093/nar/gkq486.

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