title: Release of chloroethyl ethyl sulfide-modified DNA bases by bacterial 3-methyladenine-DNA glycosylases I and II.
abstract: Treatment with chloroethyl ethyl sulfide introduces the following modified bases into DNA: 7-ethylthioethylguanine, 3-ethylthioethyladenine, and O6-ethylthioethylguanine. Using the ethylthioethylated bases as models for DNA modifications involving relatively bulky alkyl groups, we have investigated the release of these bases by Escherichia coli 3-methyladenine-DNA glycosylases I and II. 3-Methyladenine-DNA glycosylase I releases only 3-ethylthioethyladenine from chloroethyl ethyl sulfide-modified DNA, but does so at a rate which exceeds the rate of release of 3-methyladenine (m3A) from methyl nitrosourea-modified DNA under these conditions. 3-Methyladenine-DNA glycosylase II releases both 3-ethylthioethyladenine and 7-ethylthioethylguanine at rates approximating or exceeding the rate of release of m3A from methylnitrosourea-modified DNA. We conclude that these glycosylases may offer some protection against the toxicity of agents which introduce bulky groups into E. coli DNA.
authors.affiliation: Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
authors.forename: Y
authors.initials: Y
authors.lastname: Habraken
authors.forename: D B
authors.initials: DB
authors.lastname: Ludlum
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000477:Alkylating Agents / Q000378:metabolism*; D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases; D004926:Escherichia coli / Q000201:enzymology*; D008770:Methylnitrosourea / Q000378:metabolism; D009150:Mustard Compounds / Q000031:analogs & derivatives*; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology*
chemical_list: D000477:Alkylating Agents; D009150:Mustard Compounds; C025946:3-methyladenine; D008770:Methylnitrosourea; C031278:2-chloroethyl ethyl sulfide; D004247:DNA; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D000225:Adenine; D009151:Mustard Gas