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

Homology-directed repair of DNA damage has recently emerged as a major mech anism for the maintenance of genomic integrity in mammalian cells. The high ly conserved strand transferase, Rad51, is expected to be critical for this process. XRCC3 possesses a limited sequence similarity to Rad51 and intera cts with it. Using a novel fluorescence-based assay, we demonstrate here th at error-free homology-directed repair of DNA double-strand breaks is decre ased 25-fold in an XRCC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression. These results establish that XR CC3-mediated homologous recombination can reverse DNA damage that would oth erwise be mutagenic or lethal.