RRC ID 76867
Author Matsui K, Yamada M, Imai M, Yamamoto K, Nohmi T.
Title Specificity of replicative and SOS-inducible DNA polymerases in frameshift mutagenesis: mutability of Salmonella typhimurium strains overexpressing SOS-inducible DNA polymerases to 30 chemical mutagens.
Journal DNA Repair (Amst)
Abstract DNA replication is frequently hindered because of the presence of DNA lesions induced by endogenous and exogenous genotoxic agents. To circumvent the replication block, cells are endowed with multiple specialized DNA polymerases that can bypass a variety of DNA damage. To better understand the specificity of specialized DNA polymerases to bypass lesions, we have constructed a set of derivatives of Salmonella typhimurium TA1538 harboring plasmids carrying the polB, dinB or mucAB genes encoding Escherichia coli DNA polymerase II, DNA polymerase IV or DNA polymerase RI, respectively, and examined the mutability to 30 chemicals. The parent strain TA1538 possesses CGCGCGCG hotspot sequence for -2 frameshift. Interestingly, the chemicals could be classified into four groups based on the mutagenicity to the derivatives: group I whose mutagenicity was highest in strain YG5161 harboring plasmid carrying dinB; group II whose mutagenicity was almost equally high in strain YG5161 and strain TA98 harboring plasmid carrying mucAB; group III whose mutagenicity was highest in strain TA98; group IV whose mutagenicity was not affected by the introduction of any of the plasmids. Introduction of plasmid carrying polB did not enhance the mutagenicity except for benz[a]anthracene. We also introduced a plasmid carrying polA encoding E. coli DNA polymerase I to strain TA1538. Strikingly, the introduction of the plasmid reduced the mutagenicity of chemicals belonging to groups I, II and III, but not the chemicals of group IV, to the levels observed in the derivative whose SOS-inducible DNA polymerases were all deleted. These results suggest that (i) DNA polymerase IV and DNA polymerase RI possess distinct but partly overlapping specificity to bypass lesions leading to -2 frameshift, (ii) the replicative DNA polymerase, i.e., DNA polymerase III, participates in the mutagenesis and (iii) the enhanced expression of E. coli polA may suppress the access of Y-family DNA polymerases to the replication complex.
Volume 5(4)
Pages 465-78
Published 2006-4-8
DOI 10.1016/j.dnarep.2005.12.010
PII S1568-7864(05)00360-5
PMID 16455311
MeSH Benzo(a)pyrene / pharmacology DNA Polymerase I / genetics DNA Polymerase I / metabolism DNA Polymerase beta / genetics DNA Polymerase beta / metabolism DNA Replication / drug effects DNA Replication / genetics* DNA-Directed DNA Polymerase / metabolism* Enzyme Induction / drug effects Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Frameshift Mutation / drug effects* Frameshift Mutation / genetics Methylnitronitrosoguanidine / analogs & derivatives Methylnitronitrosoguanidine / pharmacology Mutagenesis / drug effects Mutagenesis / genetics Mutagens / chemistry Mutagens / pharmacology* Plasmids / genetics SOS Response, Genetics* Salmonella typhimurium / drug effects* Salmonella typhimurium / enzymology Salmonella typhimurium / genetics* Substrate Specificity
IF 3.339
Prokaryotes E. coli ME10049 ME10050