Sws1 is a conserved regulator of homologous recombination in eukaryotic cells.
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 srs2Delta and rqh1Delta mutants and rescues the inviability of srs2Delta rqh1Delta cells. Sws1 functions at an early step of recombination in a pro-recombinogenic 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.
Martín
Victoria
V
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chahwan
Charly
C
Gao
Hui
H
Blais
Véronique
V
Wohlschlegel
James
J
Yates
John R
JR
McGowan
Clare H
CH
Russell
Paul
P
D000595:Amino Acid Sequence; D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D006801:Humans; D008969:Molecular Sequence Data; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
C084232:RHP51 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C512385:Sws1 protein, S pombe; D051135:Rad51 Recombinase; D004265:DNA Helicases; C468289:Srs2 protein, S pombe