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Regulation of SOS mutagenesis by proteolysis

Frank, Ekaterina G. and Ennis, Don G. and Gonzalez, Martín and Levine, Arthur S. and Woodgate, Roger (1996) Regulation of SOS mutagenesis by proteolysis. Proceedings of the National Academy of Sciences of the United States of America, 93 (19). pp. 10291-10296. ISSN 0027-8424. https://resolver.caltech.edu/CaltechAUTHORS:20141204-103524380

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Abstract

DNA damage-inducible mutagenesis in Escherichia coli is largely dependent upon the activity of the UmuD (UmuD') and UmuC proteins. The intracellular level of these proteins is tightly regulated at both the transcriptional and the posttranslational levels. Such regulation presumably allows cells to deal with DNA damage via error-free repair pathways before being committed to error-prone pathways. We have recently discovered that as part of this elaborate regulation, both the UmuD and the UmuC proteins are rapidly degraded in vivo. We report here that the enzyme responsible for their degradation is the ATP-dependent serine protease, Lon. In contrast, UmuD' (the posttranslational product and mutagenically active form of UmuD) is degraded at a much reduced rate by Lon, but is instead rapidly degraded by another ATP-dependent protease, ClpXP. Interestingly, UmuD' is rapidly degraded by ClpXP only when it is in a heterodimeric complex with UmuD. Formation of UmuD/UmuD' heterodimers in preference to UmuD' homodimers therefore targets UmuD' protein for proteolysis. Such a mechanism allows cells to reduce the intracellular levels of the mutagenically active Umu proteins and thereby return to a resting state once error-prone DNA repair has occurred. The apparent half-life of the heterodimeric UmuD/D' complex is greatly increased in the clpX::Kan and clpP::Kan strains and these strains are correspondingly rendered virtually UV non-mutable. We believe that these phenotypes are consistent with the suggestion that while the UmuD/D' heterodimer is mutagenically inactive, it still retains the ability to interact with UmuC, and thereby precludes the formation of the mutagenically active UmuD'2C complex.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.93.19.10291DOIArticle
http://www.pnas.org/content/93/19/10291PublisherArticle
Additional Information:© 1996 National Academy of Sciences. Communicated by Evelyn M. Witkin, Rutgers, The State University of New Jersey, Piscataway, NJ, June 20, 1996 (received for review April 9, 1996). We are extremely grateful to Susan Gottesman for bacterial strains, stimulating discussions, and comments on the manuscript, and to Graham Walker for the UmuDl plasmid, pGW2053. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:UmuD/D'; UmuC; Lon; ClpXP; protein-protein interactions
Issue or Number:19
Record Number:CaltechAUTHORS:20141204-103524380
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141204-103524380
Official Citation: E G Frank, D G Ennis, M Gonzalez, A S Levine, and R Woodgate Regulation of SOS mutagenesis by proteolysis PNAS 1996 93 (19) 10291-10296
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52380
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:04 Dec 2014 18:54
Last Modified:03 Oct 2019 07:41

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