title: Mutations for Worse or Better: Low-Fidelity DNA Synthesis by SOS DNA Polymerase V Is a Tightly Regulated Double-Edged Sword.
abstract: 1953, the year of Watson and Crick, bore witness to a less acclaimed yet highly influential discovery. Jean Weigle demonstrated that upon infection of Escherichia coli, λ phage deactivated by UV radiation, and thus unable to form progeny, could be reactivated by irradiation of the bacterial host. Evelyn Witkin and Miroslav Radman later revealed the presence of the SOS regulon. The more than 40 regulon genes are repressed by LexA protein and induced by the coproteolytic cleavage of LexA, catalyzed by RecA protein bound to single-stranded DNA, the RecA* nucleoprotein filament. Several SOS-induced proteins are engaged in repairing both cellular and extracellular damaged DNA. There's no "free lunch", however, because error-free repair is accompanied by error-prone translesion DNA synthesis (TLS), involving E. coli DNA polymerase V (UmuD'2C) and RecA*. This review describes the biochemical mechanisms of pol V-mediated TLS. pol V is active only as a mutasomal complex, pol V Mut = UmuD'2C-RecA-ATP. RecA* donates a single RecA subunit to pol V. We highlight three recent insights. (1) pol V Mut has an intrinsic DNA-dependent ATPase activity that governs polymerase binding and dissociation from DNA. (2) Active and inactive states of pol V Mut are determined at least in part by the distinct interactions between RecA and UmuC. (3) pol V is activated by RecA*, not at a blocked replisome, but at the inner cell membrane.
authors.affiliation: Department of Biological Sciences, University of Southern California , Los Angeles, California 90089-0371, United States.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jaszczur
authors.affiliation: Department of Biological Sciences, University of Southern California , Los Angeles, California 90089-0371, United States.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Bertram
authors.affiliation: School of Chemistry, University of Wollongong , Wollongong, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Robinson
authors.affiliation: School of Chemistry, University of Wollongong , Wollongong, Australia.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: van Oijen
authors.affiliation: Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health , Rockville, Maryland 20850, United States.
authors.forename: Roger
authors.initials: R
authors.lastname: Woodgate
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Cox
authors.affiliation: Department of Biological Sciences, University of Southern California , Los Angeles, California 90089-0371, United States.|Department of Chemistry, University of Southern California , Los Angeles, California 90089-1062, United States.
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D011938:Rec A Recombinases / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D013014:SOS Response, Genetics; D015533:Transcriptional Activation
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D011938:Rec A Recombinases; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase; D000251:Adenosine Triphosphatases