PMID:1409640

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Citation

Matijasevic, Z, Sekiguchi, M and Ludlum, DB (1992) Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II. Proc. Natl. Acad. Sci. U.S.A. 89:9331-4

Abstract

The human carcinogen vinyl chloride is metabolized in the liver to reactive intermediates which form N2,3-ethenoguanine in DNA. N2,3-Ethenoguanine is known to cause G----A transitions during DNA replication in Escherichia coli, and its formation may be a carcinogenic event in higher organisms. To investigate the repair of N2,3-ethenoguanine, we have prepared an N2,3-etheno[14C]guanine-containing DNA substrate by nick-translating DNA with [14C]dGTP and modifying the product with chloroacetaldehyde. E. coli 3-methyladenine DNA glycosylase II, purified from cells which carry the plasmid pYN1000, releases N2,3-ethenoguanine from chloroacetaldehyde-modified DNA in a protein- and time-dependent manner. This finding widens the known substrate specificity of glycosylase II to include a modified base which may be associated with the carcinogenic process. Similar enzymatic activity in eukaryotic cell might protect them from exposure to metabolites of vinyl chloride.

Links

PubMed PMC50120

Keywords

Acetaldehyde/analogs & derivatives; Acetaldehyde/pharmacology; Carbon Radioisotopes; Chromatography, High Pressure Liquid; DNA/drug effects; DNA/metabolism; DNA Glycosylases; DNA Repair; Deoxyguanine Nucleotides/metabolism; Escherichia coli/enzymology; Guanine/analogs & derivatives; Guanine/analysis; Kinetics; Methylnitrosourea/metabolism; N-Glycosyl Hydrolases/isolation & purification; N-Glycosyl Hydrolases/metabolism; Time Factors; Tritium

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