The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae

Gaelle Lettier, Qi Feng, Adriana Antunez de Mayolo, Naz Erdeniz, Robert Reid, Michael Lisby, Uffe H. Mortensen, Rodney Rothstein
2005 PLoS Genetics  
Homologous recombination (HR) is a source of genomic instability and the loss of heterozygosity in mitotic cells. Since these events pose a severe health risk, it is important to understand the molecular events that cause spontaneous HR. In eukaryotes, high levels of HR are a normal feature of meiosis and result from the induction of a large number of DNA double-strand breaks (DSBs). By analogy, it is generally believed that the rare spontaneous mitotic HR events are due to repair of DNA DSBs
more » ... at accidentally occur during mitotic growth. Here we provide the first direct evidence that most spontaneous mitotic HR in Saccharomyces cerevisiae is initiated by DNA lesions other than DSBs. Specifically, we describe a class of rad52 mutants that are fully proficient in inter-and intra-chromosomal mitotic HR, yet at the same time fail to repair DNA DSBs. The conclusions are drawn from genetic analyses, evaluation of the consequences of DSB repair failure at the DNA level, and examination of the cellular re-localization of Rad51 and mutant Rad52 proteins after introduction of specific DSBs. In further support of our conclusions, we show that, as in wild-type strains, UVirradiation induces HR in these rad52 mutants, supporting the view that DNA nicks and single-stranded gaps, rather than DSBs, are major sources of spontaneous HR in mitotic yeast cells. Citation: Lettier G, Feng Q, Antú nez de Mayolo A, Erdeniz N, Reid RJD, et al. (2006) The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae. PLoS Genet 2(11): e194.
doi:10.1371/journal.pgen.0020194.eor fatcat:nkzavy2fifdjpeuzmwze4vyoyu