title: XRCC3 promotes homology-directed repair of DNA damage in mammalian cells.
abstract: Homology-directed repair of DNA damage has recently emerged as a major mechanism for the maintenance of genomic integrity in mammalian cells. The highly conserved strand transferase, Rad51, is expected to be critical for this process. XRCC3 possesses a limited sequence similarity to Rad51 and interacts with it. Using a novel fluorescence-based assay, we demonstrate here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XRCC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression. These results establish that XRCC3-mediated homologous recombination can reverse DNA damage that would otherwise be mutagenic or lethal.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Pierce
authors.forename: R D
authors.initials: RD
authors.lastname: Johnson
authors.forename: L H
authors.initials: LH
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Jasin
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005785:Gene Conversion; D015870:Gene Expression; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; C110901:X-ray repair cross complementing protein 3; D049452:Green Fluorescent Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase