Effect of translesion DNA polymerases, endonucleases and RpoS on mutation rates in Salmonella typhimurium.
It has been suggested that bacteria have evolved mechanisms to increase their mutation rate in response to various stresses and that the translesion DNA polymerase Pol IV under control of the LexA regulon and the alternative sigma factor RpoS are involved in regulating this mutagenesis. Here we examined in Salmonella enterica serovar Typhimurium LT2 the rates for four different types of mutations (rifampicin, nalidixic acid, and chlorate resistance and Lac(+) reversion) during various growth conditions and with different levels of four translesion DNA polymerases (Pol II, Pol IV, Pol V, and SamAB) and RpoS. Constitutive derepression of the LexA regulon by a lexA(def) mutation had no effect on Lac(+) reversion rates but increased the other three mutation rates up to 11-fold, and the contribution of the translesion DNA polymerases to this mutagenesis varied with the type of mutation examined. The increase in mutation rates in the lexA(def) mutant required the presence of the LexA-controlled UvrB protein and endonucleases UvrC and Cho. With regard to the potential involvement of RpoS in mutagenesis, neither an increase in RpoS levels conferred by artificial overexpression from a plasmid nor long-term stationary phase incubation or slow growth caused an increase in any of the four mutation rates measured, alone or in combination with overexpression of the translesion DNA polymerases. In conclusion, mutation rates are remarkably robust and no combination of growth conditions, induction of translesion DNA polymerases by inactivation of LexA, or increased RpoS expression could confer an increase in mutation rates higher than the moderate increase caused by derepression of the LexA regulon alone.
Koskiniemi
Sanna
S
Department of Cell and Molecular Biology, Uppsala University, S-75123 Uppsala, Sweden.
Hughes
Diarmaid
D
Andersson
Dan I
DI
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002704:Chlorates / Q000494:pharmacology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D009268:Nalidixic Acid / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D018085:Regulon; D012293:Rifampin / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D012697:Serine Endopeptidases / Q000378:metabolism; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D002704:Chlorates; D004259:DNA-Directed DNA Polymerase; D004720:Endonucleases; D009268:Nalidixic Acid; D019384:Nucleic Acid Synthesis Inhibitors; D012293:Rifampin; D012697:Serine Endopeptidases; D012808:Sigma Factor; D000099160:LexA Repressor Protein; C069567:sigma factor KatF protein, Bacteria