Fpg protein releases a ring-opened N-7 guanine adduct from DNA that has been modified by sulfur mustard
UMass Chan Affiliations
Department of Pharmacology and Molecular ToxicologyDocument Type
Journal ArticlePublication Date
1997-05-01Keywords
AdenineAlkylation
Carcinogens
DNA Adducts
DNA-Formamidopyrimidine Glycosylase
Escherichia coli
*Escherichia coli Proteins
Guanine
Mustard Gas
N-Glycosyl Hydrolases
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Transfection of the Escherichia coli fpg gene into Chinese hamster ovary cells has been reported to enhance survival after exposure to aziridine (C.Cussac and F.Laval, 1996, Nucleic Acids Res., 24, 1742-1746). This result suggests that Fpg protein protects cells from toxicity by removing ring-opened N-7 guanine adducts from DNA, and raises the possibility that Fpg protein would offer protection from other agents that alkylate the N-7 position of guanine. Since the major adduct formed by sulfur mustard in DNA is 7-hydroxyethyl-thioethylguanine (HETEG), we have investigated the action of Fpg protein on the ring-opened form of this adduct (ro-HETEG). A substrate containing ro-HETEG was prepared by alkaline treatment of DNA modified by [14C]sulfur mustard. Fpg protein purified from an over-producing strain of E. coli released ro-HETEG from this substrate in an enzyme- and time-dependent manner, and at a rate that is similar to that at which it releases ring-opened 7-methylguanine. Thus, Fpg protein acts efficiently on ro-HETEG, and may offer some protection against the toxic action of sulfur mustard.Source
Carcinogenesis. 1997 May;18(5):1035-8.