Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination

被引:162
作者
Alvaro, David [1 ]
Lisby, Michael [2 ]
Rothstein, Rodney [1 ]
机构
[1] Columbia Univ, Med Ctr, Dept Genet & Dev, New York, NY 10027 USA
[2] Univ Copenhagen, Dept Mol Biol, Copenhagen, Denmark
来源
PLOS GENETICS | 2007年 / 3卷 / 12期
关键词
D O I
10.1371/journal.pgen.0030228
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 rad52 Delta 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.
引用
收藏
页码:2439 / 2449
页数:11
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