Inhibition of O6-alkylguanine-DNA-alkyltransferase by metals

David A. Scicchitano, Anthony E. Pegg

Research output: Contribution to journalArticle

Abstract

The activity of the DNA-repair protein O6-alkylguanine-DNA-alkyltransferase was found to be strongly inhibited by a number of metal ions. Cd2+ was the most active followed by Cu2+, Hg2+, Zn2+ and Ag2. This inhibition is likely to result from the interaction of the metals with the cysteine-acceptor residue on the protein since the inhibition was reduced by increasing the concentration of dithiothreitol in the assay buffer. These results raise the possibility that exposure to Cd2+ could increase the mutagenicity and carcinogenicity of alkylating agents by retarding the rate of repair of alkylated DNA. However, other metals or metallic compounds which are known to be carcinogenic (such as compounds containing arsenic, lead, nickel or chromium) did not interfere with DNA repair by this protein.

Original languageEnglish (US)
Pages (from-to)207-210
Number of pages4
JournalMutation Research Letters
Volume192
Issue number3
DOIs
Publication statusPublished - 1987

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Keywords

  • Cadmium ions
  • DNA repair
  • Metal ions
  • O-Alkylguanine-DNA-alkyltransferase

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Medicine(all)
  • Molecular Biology
  • Health, Toxicology and Mutagenesis

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