XRCC3 promotes homology-directed repair of DNA damage in mammalian cells

Genes Dev. 1999 Oct 15;13(20):2633-8. doi: 10.1101/gad.13.20.2633.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • DNA Damage*
  • DNA Repair / physiology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Conversion
  • Gene Expression
  • Genetic Complementation Test
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Rad51 Recombinase
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombination, Genetic

Substances

  • DNA-Binding Proteins
  • Luminescent Proteins
  • Recombinant Proteins
  • X-ray repair cross complementing protein 3
  • Green Fluorescent Proteins
  • RAD51 protein, human
  • Rad51 Recombinase