Repair of O6-methylguanine in DNA by demethylation is lacking in Mer- human tumor cell strains

Daniel B. Yarosh, R. S. Foote, Sankar Mitra, Rufus S. Day

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

The ability of extracts of human tumor cells to demethylate O6-methylguanine (O6-MeG) in DNA was assayed using the synthetic DNA polymer poly(dC,dG,m6dG). Cell strains proficient in repair of O6-MeG in vivo (Mer+ phenotype) contained a methyltransferase activity while repair deficient cells (Mer- phenotype) had little or no activity. Mixing extracts of different Mer- strains did not result in the appearance of the activity. Extracts of Mer- cells did not inhibit the activity in extracts of Mer+ cells. Both Mer+ and Mer- strains contained methylnitrosourea-damage-specific endonuclease activity. The data suggest that the Mer- strains are deficient in methyltransferase and that this is the fundamental reason for their hypersensitivity to the cytotoxic effects of DNA alkylation. The activity was partially purified from a Mer+ colon carcinoma cell strain. Its kinetics parallel the repair of O6-MeG in DNA in vivo and suggest that the activity is inactivated during repair of DNA.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalCarcinogenesis
Volume4
Issue number2
DOIs
StatePublished - Dec 1 1983

ASJC Scopus subject areas

  • Cancer Research

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