title: An editing-defective aminoacyl-tRNA synthetase is mutagenic in aging bacteria via the SOS response.
abstract: Mistranslation in bacterial and mammalian cells leads to production of statistical proteins that are, in turn, associated with specific cell or animal pathologies, including death of bacterial cells, apoptosis of mammalian cells in culture, and neurodegeneration in the mouse. A major source of mistranslation comes from heritable defects in the editing activities of aminoacyl-tRNA synthetases. These activities clear errors of aminoacylation by deacylation of mischarged tRNAs. We hypothesized that, in addition to previously reported phenotypes in bacterial and mammalian systems, errors of aminoacylation could be mutagenic and lead to disease. As a first step in testing this hypothesis, the effect of an editing defect in a single tRNA synthetase on the accumulation of mutations in aging bacteria was investigated. A striking, statistically significant, enhancement of the mutation rate in aging bacteria was found. This enhancement comes from an increase in error-prone DNA repair through induction of the bacterial SOS response. Thus, mistranslation, as caused by an editing-defective tRNA synthetase, can lead to heritable genetic changes that could, in principle, be linked to disease.
authors.affiliation: The Skaggs Institute for Chemical Biology, and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Bacher
authors.forename: Paul
authors.initials: P
authors.lastname: Schimmel
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics*; D049148:Aminoacylation / Q000235:genetics; D018407:Bacterial Physiological Phenomena; D005815:Genetic Code; D016296:Mutagenesis; D017393:RNA Editing / Q000235:genetics*; D013014:SOS Response, Genetics / Q000502:physiology*; D013997:Time Factors
chemical_list: D000604:Amino Acyl-tRNA Synthetases