Proficient deoxyribonucleic acid repair of methylation damage in hamster ERCC-gene mutants

Publication: Research - peer-reviewJournal article – Annual report year: 1998

Without internal affiliation

DOI

  • Author: Nexø, Bjørn A.

    National Research Centre for the Working Environment

  • Author: Dybdahl, Marianne

    National Research Centre for the Working Environment

  • Author: Damgaard, Jesper

    National Research Centre for the Working Environment

  • Author: Olsen, Lone S.

    National Research Centre for the Working Environment

  • Author: Møller, Peter

    National Research Centre for the Working Environment

  • Author: Wassermann, Karsten

    National Research Centre for the Working Environment

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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.

Original languageEnglish
JournalMutation Research - DNA Repair
Volume407
Issue number3
Pages (from-to)261-268
Number of pages8
ISSN0921-8777
DOIs
StatePublished - Jun 1998
Externally publishedYes
CitationsWeb of Science® Times Cited: 1

    Keywords

  • Chinese hamster ovary cell, Colony formation, Dihydrofolate reductase, Dimethylsulfate, Gene-specific repair, Host cell reactivation, Methylnitrosourea, Nucleotide excision repair
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