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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bacher, Jamie M. Schimmel, Paul |
| Description | Author Affiliation: Bacher JM ( The Skaggs Institute for Chemical Biology, and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Amino Acyl-tRNA Synthetases Genetics Bacterial Physiological Phenomena Mutagenesis RNA Editing SOS Response (Genetics) Physiology Aminoacylation Genetic Code Time Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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