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


Authors: Akamatsu, Y.; Jasin, M.
Article Title: Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination
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 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.
Keywords: genetics; molecular genetics; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; mice, knockout; dna damage; cell survival; cells, cultured; dna repair; nuclear protein; embryonic stem cell; cell line; protein binding; camptothecin; drug effect; radiation exposure; physiology; nuclear proteins; animal embryo; genetic recombination; amino acid sequence; molecular sequence data; sequence homology, amino acid; cell culture; recombination, genetic; nucleotide sequence; fibroblast; fibroblasts; base sequence; embryonic stem cells; embryo, mammalian; multiprotein complexes; piperazines; sequence homology; piperazine derivative; two hybrid system; rad51 protein; olaparib; two-hybrid system techniques; rad51 recombinase; multiprotein complex; phthalazine derivative; rad51 protein, mouse; sfr1 protein, mouse; swi5 protein, mouse; phthalazines
Journal Title: PLoS Genetics
Volume: 6
Issue: 10
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2010-10-14
Start Page: e1001160
Language: English
PUBMED: 20976249
PROVIDER: scopus
PMCID: PMC2954829
DOI: 10.1371/journal.pgen.1001160
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "Source: Scopus"
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MSK Authors
  1. Maria Jasin
    210 Jasin