title: Roles of replicative and specialized DNA polymerases in frameshift mutagenesis: mutability of Salmonella typhimurium strains lacking one or all of SOS-inducible DNA polymerases to 26 chemicals.
abstract: Progression of DNA replication is occasionally blocked by endogenous and exogenous DNA damage. To circumvent the stalling of DNA replication, cells possess a variety of specialized DNA polymerases that replicate through DNA damage. Salmonella typhimurium strain TA1538 has six DNA polymerases and four of them are encoded by damage-inducible SOS genes, i.e. polB(ST) (pol II), dinB(ST) (pol IV), umuDC(ST) (pol V) and samAB. The strain has been used for the detection of a variety of chemical mutagens because of the high sensitivity to -2 frameshift occurring in CGCGCGCG sequence. To assign the role of each DNA polymerase in the frameshift mutagenesis, we have constructed the derivatives lacking one or all of SOS-inducible DNA polymerases and examined the mutability to 26 chemical mutagens. Interestingly, the chemicals could be categorized into four classes: class I whose mutagenicity was reduced by the deletion of dinB(ST) (1-aminoanthracene and other four chemicals); class II whose mutagenicity was reduced by the deletion of either dinB(ST) or umuDC(ST) plus samAB (7,12-dimethylbenz[a]anthracene and other three chemicals); class III whose mutagenicity largely depended on the presence of umuDC(ST) plus samAB (1-N-6-azabenzo[a]pyrene and other three chemicals) and class IV whose mutagenicity was not reduced by deletion of any of the genes encoding SOS-inducible DNA polymerases (Glu-P-1 and other 12 chemicals). Deletion of polB(ST) reduced by 30-60% the mutagenicity of six chemicals of classes II and III. These results suggest that multiple DNA polymerases including the replicative DNA polymerase, i.e. DNA polymerase III holoenzyme, play important roles in chemically induced -2 frameshift and also that different sets of DNA polymerases are engaged in the translesion bypass of different DNA lesions.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kokubo
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanke
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nohmi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D016296:Mutagenesis / Q000235:genetics / Q000502:physiology; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D010957:Plasmids / Q000235:genetics; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C094399:DinB protein, E coli; D029968:Escherichia coli Proteins; D009153:Mutagens; C074431:polB protein, E coli; C078202:UmuC protein, E coli; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli