title: Base excision repair enzyme endonuclease III suppresses mutagenesis caused by 8-hydroxy-dGTP.
abstract: To examine whether base excision repair suppresses mutations induced by oxidized deoxyribonucleotide 5'-triphosphates in the nucleotide pool, 8-hydroxy-dGTP (8-OH-dGTP) and 2-hydroxy-dATP were introduced into Escherichia coli strains deficient in endonucleases III (Nth) and VIII (Nei) and MutY, and mutations in the chromosomal rpoB gene were analyzed. The spontaneous rpoB mutant frequency was also examined in mutT/nth and mutT/nei strains, to assess the influence on the mutations induced by the endogenous 8-OH-dGTP accumulated in the mutT mutant. The mutations induced by exogenous 2-hydroxy-dATP were similar in all of the strains tested. Exogenous 8-OH-dGTP increased the rpoB mutant frequency more efficiently in the nth strain than that in the wild-type strain. The spontaneous mutant frequency in the mutT/nth strain was 2-fold higher than that in the mutT strain. These results suggest that E. coli endonuclease III also acts as a defense against the mutations caused by 8-OH-dGTP in the nucleotide pool.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiya
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004260:DNA Repair; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D016296:Mutagenesis; D010084:Oxidation-Reduction
chemical_list: C521293:8-hydroxy-2'-deoxyguanosine 5'-triphosphate; D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli