Poster Abstract

May 7, 2010

Rad51 Inhibits Translocation Formation by Non-conservative Homologous Recombination in Saccharomyces cerevisiae

Dr. Adam Bailis
Department of Molecular and Cellular Biology
City of Hope

Abstract: Chromosomal translocations are a primary biological response to ionizing radiation exposure, and are likely to result from the repair of the DNA double-strand breaks (DSBs) that are created. The profusion of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms. In particular, Rad51 suppresses translocation formation by single-strand annealing (SSA), perhaps the most efficient mechanism for translocation formation by HR in both yeast and mammalian cells. Further, the enhanced translocation formation that emerges in the absence of Rad51 displays a distinct pattern of genetic control, suggesting that this occurs by a novel, separate mechanism. Recent papers from the Bailis lab describing work on translocation formation by homologous recombination: 1. Pannunzio NR, Manthey GM, Bailis AM. 2010 RAD59 and RAD1 cooperate in translocation formation by single-strand annealing in Saccharomyces cerevisiae. Curr Genet. 56(1):87-100. PMID: 20012294 2. Manthey GM, Naik N, Bailis AM 2009 Msh2 blocks an alternative mechanism for non-homologous tail removal during single-strand annealing in Saccharomyces cerevisiae. PLoS One. 4(10):e7488.PMID: 19834615 3. Meyer DH, Bailis AM. 2008 Telomerase deficiency affects the formation of chromosomal translocations by homologous recombination in Saccharomyces cerevisiae. PLoS One 3(10):e3318.PMID: 18830407 4. Pannunzio NR, Manthey GM, Bailis AM. 2008 RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae. DNA Repair (Amst). 7(5):788-800. PMID: 18373960 Paper describing efficient translocation formation in yeast by HR between repeated sequences following acute radiation exposure: 1.Argueso JL, Westmoreland J, Mieczkowski PA, Gawel M, Petes TD, Resnick MA. 2008 Double-strand breaks associated with repetitive DNA can reshape the genome.Proc Natl Acad Sci U S A.105(33):11845-11850. PMID: 18701715 Paper describing the effects of hypomorphic mutations in RAD51 and BRCA2 on repair of DSBs by conservative and non-conservative repair in mouse cells: 1. Stark JM, Pierce AJ, Oh J, Pastink A, Jasin M. 2004 Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol. 24(21):9305-9316. PMID: 15485900