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 ovary cells of complementation group 1. To investigate the involvement of the ERCC-1 gene in gene-specific repair of bulky lesions, we have studied 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 cisplatin and found efficient removal of ICLs from the dihydrofolate reductase (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) induced by cisplatin. Compared to the wild-type parental cell line, the ERCC-1 transfected 43-3B cells repaired the IAs in the DHFR gene inefficiently. Thus, our data suggest that the ERCC-1 gene is more involved in the repair of interstrand crosslinks than in the removal of intrastrand adducts.
Larminat
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Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, MD 21224.
Bohr
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VA
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004720:Endonucleases; D006801:Humans; D009154:Mutation; D009691:Nucleic Acid Denaturation; D009695:Nucleic Acid Renaturation; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014162:Transfection
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D011506:Proteins; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin