Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code
- Ohio State University, United States
- Adana Military Hospital, Turkey
- Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
- California Department of Toxic Substances Control, United States
- University of California, Los Angeles, United States
Abstract
Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost versus benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability.
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© 2014, Bullwinkle et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code
eLife 3:e02501.
https://doi.org/10.7554/eLife.02501
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