Title

Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

1992-10-01

Document Type

Article

Subjects

Acetaldehyde; Carbon Radioisotopes; Chromatography, High Pressure Liquid; DNA; *DNA Glycosylases; DNA Repair; Deoxyguanine Nucleotides; Escherichia coli; Guanine; Kinetics; Methylnitrosourea; N-Glycosyl Hydrolases; Time Factors; Tritium

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Source

Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9331-4.

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID

1409640

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