title: Insights into the complex levels of regulation imposed on Escherichia coli DNA polymerase V.
abstract: It is now close to 40 years since the isolation of non-mutable umu/uvm strains of Escherichia coli and the realization that damage induced mutagenesis in E.coli is not a passive process. Early models of mutagenesis envisioned the Umu proteins as accessory factors to the cell's replicase that not only reduced its normally high fidelity, but also allowed the enzyme to traverse otherwise replication-blocking lesions in the genome. However, these models underwent a radical revision approximately 15 years ago, with the discovery that the Umu proteins actually encode for a DNA polymerase, E.coli pol V. The polymerase lacks 3'→5' exonucleolytic proofreading activity and is inherently error-prone when replicating both undamaged and damage DNA. So as to limit any "gratuitous" mutagenesis, the activity of pol V is strictly regulated in the cell at multiple levels. This review will summarize our current understanding of the myriad levels of regulation imposed on pol V including transcriptional control, posttranslational modification, targeted proteolysis, activation of the catalytic activity of pol V through protein-protein interactions and the very recently described intracellular spatial regulation of pol V. Remarkably, despite the multiple levels at which pol V is regulated, the enzyme is nevertheless able to contribute to the genetic diversity and evolutionary fitness of E.coli.
authors.affiliation: Departments of Biological Sciences and Chemistry, University of Southern California, University Park, Los Angeles, CA 90089-2910, USA. Electronic address: mgoodman@usc.edu.
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
authors.affiliation: Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: McDonald
authors.affiliation: Department of Biological Sciences, University of Southern California, University Park, Los Angeles, CA 90089-2910, USA.
authors.forename: Malgorzata M
authors.initials: MM
authors.lastname: Jaszczur
authors.affiliation: Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA. Electronic address: woodgate@mail.nih.gov.
authors.forename: Roger
authors.initials: R
authors.lastname: Woodgate
mesh_terms: D004249:DNA Damage; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D056084:Genetic Fitness; D014644:Genetic Variation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D013014:SOS Response, Genetics
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C078202:UmuC protein, E coli; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli; C483573:ClpXP protease, E coli; D049071:Endopeptidase Clp
keywords: Posttranslational regulation; Proteolysis; Translesion DNA synthesis; Y-family DNA polymerase