PROFICIENT DEOXYRIBONUCLEIC-ACID REPAIR OF METHYLATION DAMAGE IN HAMSTER ERCC-GENE MUTANTS

Three major pathways, nucleotide excision repair (NER), base excision repair (BER) and O-6-methylguanine-DNA methyltransferase (MGMT), are r esponsible for the removal of most adducts to DNA and thus for the sur vival of cells influenced by deoxyribonucleic acid (DNA) adduct-formin g chemicals. We have evaluated host cell reactivation and cell surviva l of wild type Chinese hamster ovary cells and of mutants in the NER-g enes ERCC1, ERCC2, and ERCC4 after treatment with the methylating comp ounds dimethylsulfate and methylnitrosourea. No effect of the three ge nes could be demonstrated, i.e., survival and host cell reactivation a fter methylation damage in the mutants and the wild type cells were si milar. Gene-specific repair experiments confirmed the proficient remov al of methyl lesions. We conclude that the three nucleotide excision r epair genes are immaterial to the repair of methylation damage. This s uggests that NER does not play a role in the removal of methylation in mammalian cells and that BER and MGMT are responsible for the surviva l of such cells, when they are challenged with methylation of DNA. (C) 1998 Elsevier Science B.V. All rights reserved.