Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II
Department of Pharmacology and Molecular Toxicology; Department of Cell Biology
DNA Adducts; *DNA Glycosylases; DNA Repair; Escherichia coli; *Mustard Gas; N-Glycosyl Hydrolases; Substrate Specificity
Life Sciences | Medicine and Health Sciences
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.
Carcinogenesis. 1996 Oct;17(10):2249-52.
Matijasevic, Zdenka; Stering, Allen; Niu, Tian-Qi; Austin-Ritchie, Paula; and Ludlum, David B., "Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II" (1996). Open Access Articles. 384.