genome-wide analysis of rad52 foci reveals diverse mechanisms impacting recombination全基因组分析rad52焦点显示不同机制影响重组.pdfVIP

Genome-Wide Analysis of Rad52 Foci Reveals Diverse Mechanisms Impacting Recombination 1 2 1* David Alvaro , Michael Lisby , Rodney Rothstein 1 Department of Genetics and Development, Columbia University Medical Center, New York, New York, United States of America, 2 Department of Molecular Biology, University of Copenhagen, Copenhagen, Denmark To investigate the DNA damage response, we undertook a genome-wide study in Saccharomyces cerevisiae and identified 86 gene deletions that lead to increased levels of spontaneous Rad52 foci in proliferating diploid cells. More than half of the genes are conserved across species ranging from yeast to humans. Along with genes involved in DNA replication, repair, and chromatin remodeling, we found 22 previously uncharacterized open reading frames. Analysis of recombination rates and synthetic genetic interactions with rad52D suggests that multiple mechanisms are responsible for elevated levels of spontaneous Rad52 foci, including increased production of recombinogenic lesions, sister chromatid recombination defects, and improper focus assembly/disassembly. Our cell biological approach demonstrates the diversity of processes that converge on homologous recombination, protect against spontaneous DNA damage, and facilitate efficient repair. Citation: Alvaro D, Lisby M, Rothstein R (2007) Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination. PLoS Genet 3(12): e228. doi:10. 1371/journal.pgen.0030228 Introduction activated to arrest cell cycle progression until completion of repair. The lesion is repaired through HR performed b