Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination.
The repair of DNA double-strand breaks is essential for cells to maintain their genomic integrity. Two major mechanisms are responsible for repairing these breaks in mammalian cells, non-homologous end-joining (NHEJ) and homologous recombination (HR): the importance of the former in mammalian cells is well established, whereas the role of the latter is just emerging. Homologous recombination is presumably promoted by an evolutionarily conserved group of genes termed the Rad52 epistasis group. An essential component of the HR pathway is the strand-exchange protein, known as RecA in bacteria or Rad51 in yeast. Several mammalian genes have been implicated in repair by homologous recombination on the basis of their sequence homology to yeast Rad51: one of these is human XRCC2. Here we show that XRCC2 is essential for the efficient repair of DNA double-strand breaks by homologous recombination between sister chromatids. We find that hamster cells deficient in XRCC2 show more than a 100-fold decrease in HR induced by double-strand breaks compared with the parental cell line. This defect is corrected to almost wild-type levels by transient transfection with a plasmid expressing XRCC2. The repair defect in XRCC2 mutant cells appears to be restricted to recombinational repair because NHEJ is normal. We conclude that XRCC2 is involved in the repair of DNA double-strand breaks by homologous recombination.
Johnson
R D
RD
Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.
Liu
N
N
Jasin
M
M
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019868:Kanamycin Kinase / Q000235:genetics; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human; D004247:DNA; D019868:Kanamycin Kinase; C495153:RAD51 protein, human; D051135:Rad51 Recombinase