ROLE OF THE HUMAN ERCC-1 GENE IN GENE-SPECIFIC REPAIR OF CISPLATIN-INDUCED DNA-DAMAGE

The human excision repair gene ERCC-1 gene restores normal resistance to UV and mitomycin C in excision repair deficient chinese hamster ova ry cells of complementation group 1. To investigate the involvement of the ERCC-1 gene in gene-specific repair of bulky lesions, we have stu died the removal of damage induced by the antitumor agent cisplatin in CHO mutant 43-3B cells of group 1, with or without transfection with the ERCC-1 gene. Firstly, we determined the contribution of the ERCC-1 gene to the repair of interstrand crosslinks (ICL) induced by cisplat in and found efficient removal of ICLs from the dihydrofolate reductas e (DHFR) gene in the ERCC-1 transfected 43-3B cells. We then assessed the contribution of ERCC-1 to the repair of intrastrand adducts (IA) i nduced by cisplatin. Compared to the wild-type parental cell line, the ERCC-1 transfected 43-3B cells repaired the IAs in the DHFR gene inef ficiently. Thus, our data suggest that the ERCC-1 gene is more involve d in the repair of interstrand crosslinks than in the removal of intra strand adducts.