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

  1. Andrew J. Pierce,
  2. Roger D. Johnson,
  3. Larry H. Thompson, and
  4. Maria Jasin
  1. Cell Biology Program, Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, New York 10021 USA; Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94551 USA

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.

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Footnotes

  • Corresponding author.

  • E-MAIL m-jasin{at}ski.mskcc.org; FAX (212) 717-3317.

    • Received July 22, 1999.
    • Accepted August 27, 1999.
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