role for the mammalian swi5-sfr1 complex in dna strand break repair through homologous recombination作用的哺乳动物swi5-sfr1复杂dna链断裂通过同源重组修复.pdfVIP

Role for the Mammalian Swi5-Sfr1 Complex in DNA Strand Break Repair through Homologous Recombination Yufuko Akamatsu, Maria Jasin* Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America Abstract 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 strand- exchange protein which functions during HR. By generating Swi52/ 2 and Sfr1 2/ 2 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. Swi52/ 2 and Sfr12/ 2 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 Swi52/ 2 and Sfr12/ 2 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. Citation: Akamatsu Y, Jasin M (2010) Role for the Mammalian Swi5-Sfr1 Complex in DNA Strand Break Repair through Homologous Recombination. PLoS Genet 6(10): e1001160. doi:10.1371/journal.pgen.1001160 Editor: James E. Haber, Brandeis University, United States of America Received July 27, 2010; Accepted September 15, 2010; Published October 14, 2010 Copyright: 2010 Akamatsu, Jasin. This is an open-acc