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Nucleic Acids Research, 1994, Vol. 22, No. 15 3005-3010
© 1994


MOLECULAR BIOLOGY

Role of the human ERCC-1 gene in gene-specific repair of cisplatin-induced DNA damage

Florence Larminat+ and Vilhelm A. Bohr*

Laboratory of Molecular Genetics, National Institute on Aging NIH, 4940 Eastern Avenue, Baltimore, MD 21224, USA

*To whom correspondence should be addressed

Received May 13, 1994. Revised June 20, 1994. Accepted June 20, 1994.

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 lAs 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.


+Present address: Laboratoire de Pharmacologie et de Toxicologie Fondamentales, 205 Route de Narbonne, 31077 Toulouse Cedex, France


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