RRC ID 76866
Author Kokubo K, Yamada M, Kanke Y, Nohmi T.
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.
Journal DNA Repair (Amst)
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.
Volume 4(10)
Pages 1160-71
Published 2005-9-28
DOI 10.1016/j.dnarep.2005.06.016
PII S1568-7864(05)00190-4
PMID 16103022
MeSH Alcohol Oxidoreductases / genetics Bacterial Proteins / genetics Bacterial Proteins / physiology* DNA Damage / genetics DNA Replication* / genetics DNA-Directed DNA Polymerase / genetics DNA-Directed DNA Polymerase / physiology* Escherichia coli Proteins / genetics Frameshift Mutation* Gene Deletion Mutagenesis / genetics Mutagenesis / physiology Mutagens / chemistry Mutagens / toxicity Plasmids / genetics SOS Response, Genetics* Salmonella typhimurium / drug effects Salmonella typhimurium / enzymology Salmonella typhimurium / genetics*
IF 3.339
Prokaryotes E. coli ME10048 ME10052 ME10053 ME10054