Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II.
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.
Matijasevic
Z
Z
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Sekiguchi
M
M
Ludlum
D B
DB
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D007700:Kinetics; D008770:Methylnitrosourea / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000302:isolation & purification / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D002250:Carbon Radioisotopes; D003848:Deoxyguanine Nucleotides; C015196:N(2),3-ethenoguanine; D014316:Tritium; D006147:Guanine; D008770:Methylnitrosourea; C029603:deoxyguanosine triphosphate; D004247:DNA; C004656:chloroacetaldehyde; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C076131:DNA-3-methyladenine glycosidase II; D000079:Acetaldehyde