PMID:11812126

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Citation

Balashov, S and Humayun, MZ (2002) Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells. J. Mol. Biol. 315:513-27

Abstract

Translational stress-induced mutagenesis (TSM) refers to the mutator phenotype observed in Escherichia coli cells expressing a mutant allele (mutA or mutC) of the glycine tRNA gene glyV (or glyW). Because of an anticodon mutation, expression of the mutA allele results in low levels of Asp-->Gly mistranslation. The mutA phenotype does not require lexA-regulated SOS mutagenesis functions, and appears to be suppressed in cells defective for RecABC-dependent homologous recombination functions. To test the hypothesis that the TSM response is mediated by non-specific mistranslation rather than specific Asp-->Gly misreading, we asked if streptomycin (Str), an aminoglycoside antibiotic known to promote mistranslation, can provoke a mutator phenotype. We report that Str induces a strong mutator phenotype in cells bearing certain alleles of rpsL, the gene encoding S12, an essential component of the ribosomal 30 S subunit. The phenotype is strikingly similar to that observed in mutA cells in its mutational specificity, as well as in its requirement for RecABC-mediated homologous recombination functions. Expression of Str-inducible mutator phenotype correlates with mistranslation efficiency in response to Str. Thus, mistranslation in general is able to induce the TSM response. The Str-inducible mutator phenotype described here defines a new functional class of rpsL alleles, and raises interesting questions on the mechanism of action of Str, and on bacterial response to antibiotic stress.

Links

PubMed Online version:10.1006/jmbi.2001.5273

Keywords

Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Codon, Nonsense/genetics; DNA Helicases; DNA-Binding Proteins/metabolism; Dose-Response Relationship, Drug; Drug Resistance, Bacterial/genetics; Endodeoxyribonucleases/metabolism; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/metabolism; Exodeoxyribonuclease V; Exodeoxyribonucleases/metabolism; Gene Expression Regulation, Bacterial/drug effects; Gene Frequency; Lac Operon/genetics; Mutagenesis/drug effects; Mutagenesis/genetics; Phenotype; Protein Biosynthesis/drug effects; Protein Biosynthesis/genetics; Protein Synthesis Inhibitors/pharmacology; Rec A Recombinases/metabolism; Recombination, Genetic/genetics; Regulon/genetics; SOS Response (Genetics)/genetics; Sequence Homology, Nucleic Acid; Serine Endopeptidases/genetics; Streptomycin/pharmacology; Suppression, Genetic/genetics

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