Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination

In fission yeast,the swi5-sfr1 complex plays an important role in homologous recombination (hr),a pathway crucial for the maintenance of genomic integrity. here we identify and characterize mammalian swi5 and sfr1 homologues. mouse swi5 and sfr1 are nuclear proteins that form a complex in vivo and in vitro. swi5 interacts in vitro with rad51,the dna strandexchange protein which functions during hr. by generating swi5-/- and sfr1-/- embryonic stem cell lines,we found that both proteins are mutually interdependent for their stability. importantly,the swi5-sfr1 complex plays a role in hr when rad51 function is perturbed in vivo by expression of a brc peptide from brca2. swi5-/- and sfr1-/- cells are selectively sensitive to agents that cause dna strand breaks,in particular ionizing radiation,camptothecin,and the parp inhibitor olaparib. consistent with a role in hr,sister chromatid exchange induced by parp inhibition is attenuated in swi5-/- and sfr1-/- cells,and chromosome aberrations are increased. thus,swi5-sfr1 is a newly identified complex required for genomic integrity in mammalian cells with a specific role in the repair of dna strand breaks. © 2010 akamatsu,jasin.