title: Proficient deoxyribonucleic acid repair of methylation damage in hamster ERCC-gene mutants.
abstract: Three major pathways, nucleotide excision repair (NER), base excision repair (BER) and O6-methylguanine-DNA methyltransferase (MGMT), are responsible for the removal of most adducts to DNA and thus for the survival of cells influenced by deoxyribonucleic acid (DNA) adduct-forming chemicals. We have evaluated host cell reactivation and cell survival of wild type Chinese hamster ovary cells and of mutants in the NER-genes ERCC1, ERCC2, and ERCC4 after treatment with the methylating compounds dimethylsulfate and methylnitrosourea. No effect of the three genes could be demonstrated, i.e., survival and host cell reactivation after methylation damage in the mutants and the wild type cells were similar. Gene-specific repair experiments confirmed the proficient removal of methyl lesions. We conclude that the three nucleotide excision repair genes are immaterial to the repair of methylation damage. This suggests that NER does not play a role in the removal of methylation in mammalian cells and that BER and MGMT are responsible for the survival of such cells, when they are challenged with methylation of DNA.
authors.affiliation: National Institute of Occupational Health, Copenhagen, Denmark.
authors.forename: B A
authors.initials: BA
authors.lastname: Nexø
authors.forename: M
authors.initials: M
authors.lastname: Dybdahl
authors.forename: J
authors.initials: J
authors.lastname: Damgaard
authors.forename: L S
authors.initials: LS
authors.lastname: Olsen
authors.forename: P
authors.initials: P
authors.lastname: Møller
authors.forename: K
authors.initials: K
authors.lastname: Wassermann
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018736:DNA Adducts / Q000235:genetics; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases; D005260:Female; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011506:Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases