THE XRCC2 DNA-REPAIR GENE - IDENTIFICATION OF A POSITIONAL CANDIDATE

The human XRCC2 gene, complementing a hamster cell line (irs1) hyperse nsitive to DNA-damaging agents, was previously mapped to chromosome 7q 36.1. Following radiation reduction of human/hamster hybrids, the gene was found to be associated with the marker D7S483. Yeast artificial c hromosomes (YACs) carrying D7S483 were fused to the irs1 cell line to identify a YAC that complemented the sensitivity defect, Transcribed s equences were isolated by direct cDNA selection using the complementin g YAC, and these were mapped back to the YAC and hybrids to define a 4 00-kb region carrying XRCC2. Sequencing of cDNAs led to the identifica tion of both known and novel gene sequences, including a candidate for XRCC2 with homology to the yeast RAD51 gene involved in the recombina tional repair of DNA damage. Strong support for the candidacy of this gene was obtained from its refined map position and by the full comple mentation of irs1 sensitivity with a 40-kb cosmid carrying the gene. ( C) 1997 Academic Press.