Sws1 is a conserved regulator of homologous recombination in eukaryotic cells

被引:95
作者
Martin, Victoria
Chahwan, Charly
Gao, Hui
Blais, Veronique
Wohlschlegel, James
Yates, John R., III
McGowan, Clare H.
Russell, Paul
机构
[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
关键词
DNA repair; genome stability; homologous recombination;
D O I
10.1038/sj.emboj.7601141
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rad52-dependent homologous recombination ( HR) is regulated by the antirecombinase activities of Srs2 and Rqh1/Sgs1 DNA helicases in fission yeast and budding yeast. Functional analysis of Srs2 in Schizosaccharomyces pombe led us to the discovery of Sws1, a novel HR protein with a SWIM-type Zn finger. Inactivation of Sws1 suppresses the genotoxic sensitivity of srs2 Delta and rqh1 Delta mutants and rescues the inviability of srs2 Delta rqh1 Delta cells. Sws1 functions at an early step of recombination in a prorecombinogenic complex with Rlp1 and Rdl1, two RecA-like proteins that are most closely related to the human Rad51 paralogs XRCC2 and RAD51D, respectively. This finding indicates that the XRCC2-RAD51D complex is conserved in lower eukaryotes. A SWS1 homolog exists in human cells. It associates with RAD51D and ablating its expression reduces the number of RAD51 foci. These studies unveil a conserved pathway for the initiation and control of HR in eukaryotic cells.
引用
收藏
页码:2564 / 2574
页数:11
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