XRCC2 AND XRCC3, NEW HUMAN RAD51-FAMILY MEMBERS, PROMOTE CHROMOSOME STABILITY AND PROTECT AGAINST DNA CROSS-LINKS AND OTHER DAMAGES

The phenotypically similar hamster mutants irs1 and irs1SF exhibit hig h spontaneous chromosome instability and broad-spectrum mutagen sensit ivity, including extreme sensitivity to DNA cross-linking agents. The human XRCC2 and XRCC3 genes, which functionally complement irs1 and ir s1SF, respectively, were previously mapped in somatic cell hybrids. Ch aracterization of these genes and sequence alignments reveal that XRCC 2 and XRCC3 are members of an emerging family of Rad51-related protein s that likely participate in homologous recombination to maintain chro mosome stability and repair DNA damage. XRCC3 is shown to interact dir ectly with HsRad51, and like Rad55 and Rad57 in yeast, may cooperate w ith HsRad51 during recombinational repair. Analysis of the XRCC2 mutat ion in irs1 implies that XRCC2's function is not essential for viabili ty in cultured hamster cells.