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BIOLOGICAL SCIENCES / GENETICS
An editing-defective aminoacyl-tRNA synthetase is mutagenic in aging bacteria via the SOS response
The Skaggs Institute for Chemical Biology, and Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC-379, La Jolla, CA 92037
Contributed by Paul Schimmel, December 6, 2006 (received for review November 30, 2006)
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.
aminoacylation errors | error-prone DNA polymerases | amino acid misincorporation | genetic code ambiguity
The authors declare no conflict of interest.
*To whom correspondence should be addressed. E-mail: schimmel{at}scripps.edu
© 2007 by The National Academy of Sciences of the USA
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