Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II.
The toxic effects of sulfur mustard have been attributed to DNA modification with the formation of 7-hydroxyethylthioethyl guanine, 3-hydroxyethylthioethyl adenine and the cross-link, di-(2-guanin-7-yl-ethyl)sulfide. To investigate the action of bacterial 3-methyladenine DNA glycosylase II (Gly II) on these adducts, calf thymus DNA was modified with [14C]sulfur mustard and used as a substrate for Gly II. Gly II releases both 3-hydroxyethylthioethyl adenine and 7-hydroxyethylthioethyl guanine from this substrate. In comparison with the activity of Gly II towards methylated DNA, 3-hydroxyethylthioethyl adenine is released somewhat more slowly than 3-methyladenine, while 7-hydroxyethylthioethyl guanine is released much more readily than 7-methylguanine. Glycosylase action may play a role in protecting cells from the toxic effects of sulfur mustard.
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655-0126, USA.
Z
Z
Matijasevic
A
A
Stering
T Q
TQ
Niu
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P
Austin-Ritchie
D B
DB
Ludlum
D018736:DNA Adducts / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology; D009151:Mustard Gas; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D013379:Substrate Specificity
D018736:DNA Adducts; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C076131:DNA-3-methyladenine glycosidase II; D009151:Mustard Gas