X-Ray Repair Cross Complementing 3 (XRCC3)
encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. These results indicated that XRCC3 function is not limited to HR initiation, but extends to later stages in formation and resolution of HR intermediates, possibly by stabilizing heteroduplex DNA. The results further demonstrated that HR defects can promote genomic instability not only through failure to initiate HR, but also through aberrant processing of HR intermediates. The authors suggested that both mechanisms may contribute to carcinogenesis in HR-deficient cells.