title: Mutation rate is reduced by increased dosage of mutL gene in Escherichia coli K-12.
abstract: A variable but substantial proportion of wild Escherichia coli isolates present consistently lower mutation frequencies than that found in the ensemble of strains. The genetic mechanisms responsible for the hypo-mutation phenotype are much less known than those involved in hyper-mutation. Changes in E. coli mutation frequencies derived from the gene-copy effect of mutS, mutL, mutH, uvrD, mutT, mutY, mutM, mutA, dnaE, dnaQ, and rpoS are explored. When present in a very high copy number ( approximately 300 copies cell(-1)), mutL, mutH, and mutA gene copies yielded >/=twofold decrease in mutation rates determined by Luria-Delbrück fluctuation tests. Nevertheless, when the copy number was not such high ( approximately 15 copies cell(-1)), only mutL results in a consistent twofold decrease in the mutation rate. This reduction seems to be independent from the RecA background, phase of growth, or from the presence of proficient MutS. An increase in mutL gene copies was also able to partially compensate the hypermutator phenotype of a mutS-defective E. coli derivative.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal (Unidad Asociada al CSIC Resistencia a Antibióticos y Virulencia Bacteriana) and CIBER-ESP, Madrid, Spain. jgalanm.hrc@salud.madrid.org
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Galán
authors.forename: María-Carmen
authors.initials: MC
authors.lastname: Turrientes
authors.forename: María-Rosario
authors.initials: MR
authors.lastname: Baquero
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Alcayna
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez-Amado
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Martínez
authors.forename: Fernando
authors.initials: F
authors.lastname: Baquero
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D020137:Base Pair Mismatch; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D048168:Escherichia coli K12 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology