title: Excision of the imidazole ring-opened form of N-2-aminofluorene-C(8)-guanine adduct in poly(dG-dC) by Escherichia coli formamidopyrimidine-DNA glycosylase.
abstract: A polynucleotide containing N-(deoxyguanosine-8-yl)-2-aminofluorene residues (dGuo-C8-AF) was obtained by treatment of poly(dG-dC) with [3H]ring-N-hydroxy-2-amino-fluorene. This substrate was further treated under alkaline conditions to convert dGuo-C8-AF residues into their imidazole ring-opened derivative or 1-[6-(2,5-diamino-4-oxo-pyrimidinyl-N-6-deoxyribose]-3-(2-fluorenyl++ +)urea (iro-dGuo-C8-AF). The ring-opening of 50% of the dGuo-C8-AF residues occurs in 24 h at 37 degrees C in the presence of 0.1 N NaOH. This modified polynucleotide was used as substrate for the homogeneous formamidopyrimidine-DNA glycosylase (Fapy-DNA glycosyase) of Escherichia coli. Analysis of the reaction products shows that Fapy-DNA glycosylase releases the imidazole ring-opened derivative (iro-G-C8-AF). In contrast the primary adduct (G-C8-AF) is not removed. These results show that the imidazole ring-opened form of guanine residue modified at the C8 position by a bulky adduct is a substrate for the formamidopyrimidine-DNA glycosylase of E. coli. These observations show that the formamidopyrimidine-DNA glycosylase has a broad substrate specificity including imidazole ring-opened purines either modified at N7 or C8 positions in DNA. Therefore, the Fapy-DNA glycosylase might be involved in the repair of minor lesions induced by many chemical carcinogens.
authors.affiliation: Groupe 'Réparation des lésions radio- et chimioinduites' URA 158 CNRS, 140 INSERM, Institut Gustave Roussy, France.
authors.forename: S
authors.initials: S
authors.lastname: Boiteux
authors.forename: M
authors.initials: M
authors.lastname: Bichara
authors.forename: R P
authors.initials: RP
authors.lastname: Fuchs
authors.forename: J
authors.initials: J
authors.lastname: Laval
mesh_terms: D043382:DNA-Formamidopyrimidine Glycosylase; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins; D005449:Fluorenes; D006147:Guanine; D007700:Kinetics; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D011089:Polydeoxyribonucleotides
chemical_list: D029968:Escherichia coli Proteins; D005449:Fluorenes; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); C012177:2-aminofluorene; D006147:Guanine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli