SOS Mutator DNA Polymerase IV Functions in Adaptive Mutation and Not Adaptive Amplification

McKenzie, Gregory J.; Lee, Peter L.; Lombardo, Mary Jane; Hastings, P. J.; Rosenberg, Susan M.

doi:10.1016/s1097-2765(01)00204-0

Cited by 270 publications

(314 citation statements)

References 58 publications

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“…Indeed, a number of the cassettes listed in Supplementary Table S3 were shared (amino acid BSR values 40.70) exclusively between Vibrio mucus cultivars, known coral pathogens and known human pathogens including V. vulnificus and V. cholerae. These cassetteencoded functions include putative resistance genes, specifically glyoxalases/bleomycin resistance, three different acetyltransferases and DinB, the damageinducible protein, which is triggered during bacterial SOS response and has the potential to increase mutation rate (McKenzie et al, 2001) and, potentially, the rate of cassette rearrangements (Guerin et al, 2009).…”

Section: Pocillopora Damicornis Mucus Contains a Variety Ofmentioning

confidence: 99%

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

et al. 2011

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Integron cassette arrays in a dozen cultivars of the most prevalent group of Vibrio isolates obtained from mucus expelled by a scleractinian coral (Pocillopora damicornis) colony living on the Great Barrier Reef were sequenced and compared. Although all cultivars showed 499% identity across recA, pyrH and rpoB genes, no two had more than 10% of their integron-associated gene cassettes in common, and some individuals shared cassettes exclusively with distantly-related members of the genus. Of cassettes shared within the population, a number appear to have been transferred between Vibrio isolates, as assessed by phylogenetic analysis. Prominent among the mucus Vibrio cassettes with potentially inferable functions are acetyltransferases, some with close similarity to known antibiotic-resistance determinants. A subset of these potential resistance cassettes were shared exclusively between the mucus Vibrio cultivars, Vibrio coral pathogens and human pathogens, thus illustrating a direct link between these microbial niches through exchange of integron-associated gene cassettes.

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Section: Pocillopora Damicornis Mucus Contains a Variety Ofmentioning

confidence: 99%

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

et al. 2011

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“…The rate of adaptive mutation is reduced two-to four-fold if Pol IV is eliminated [57,58]. E. coli's other inducible error-prone polymerase, Pol V, is not involved in adaptive mutation [36,59].…”

Section: The Genetics Of Adaptive Mutationmentioning

confidence: 99%

Stress responses and genetic variation in bacteria

Foster

2005

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

173

106

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Under stressful conditions mechanisms that increase genetic variation can bestow a selective advantage. Bacteria have several stress responses that provide ways in which mutation rates can be increased. These include the SOS response, the general stress response, the heat-shock response, and the stringent response, all of which impact the regulation of error-prone polymerases. Adaptive mutation appears to be process by which cells can respond to selective pressure specifically by producing mutations. In Escherichia coli strain FC40 adaptive mutation involves the following inducible components: (i) a recombination pathway that generates mutations; (ii) a DNA polymerase that synthesizes error-containing DNA; and (iii) stress responses that regulate cellular processes. In addition, a subpopulation of cells enters into a state of hypermutation, giving rise to about 10% of the single mutants and virtually all of the mutants with multiple mutations. These bacterial responses have implications for the development of cancer and other genetic disorders in higher organisms.

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“…SMR 4562 is an independent isolate of FC40 [26]. SMR 5830 is isogenic to SMR4562, and is dinB10 [F'dinB10] [27]. Spontaneous 5-flourouracil-resistant, 5-fluoro-2'deoxythymidine (FUdR)-resistant isolates of both strains were isolated by selective plating as previously described [28].…”

Section: Escherichia Coli Strainsmentioning

confidence: 99%

Escherichia coli DNA polymerase IV contributes to spontaneous mutagenesis at coding sequences but not microsatellite alleles

Jacob

Eckert

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Slipped strand mispairing during DNA synthesis is one proposed mechanism for microsatellite or short tandem repeat (STR) mutation. However, the DNA polymerase(s) responsible for STR mutagenesis have not been determined. In this study, we investigated the effect of the Escherichia coli dinB gene product (Pol IV) on mononucleotide and dinucleotide repeat stability, using an HSVtk gene episomal reporter system for microsatellite mutations. For the control vector (HSV-tk gene only) we observed a statistically significant 3.5-fold lower median mutation frequency in dinB -than dinB + cells (p<0.001, Wilcoxon Mann Whitney Test). For vectors containing an in-frame mononucleotide allele ([G/C] 10 ) or either of two dinucleotide alleles ([GT/CA] 10 and [TC/AG] 11 ) we observed no statistically significant difference in the overall HSV-tk mutation frequency observed between dinB + and dinB -strains. To determine if a mutational bias exists for mutations made by Pol IV, mutational spectra were generated for each STR vector and strain. No statistically significant differences between strains were observed for either the proportion of mutational events at the STR or STR specificity among the three vectors. However, the specificity of mutational events at the STR alleles in each strain varied in a statistically significant manner as a consequence of microsatellite sequence. Our results indicate that while Pol IV contributes to spontaneous mutations within the HSV-tk coding sequence, Pol IV does not play a significant role in spontaneous mutagenesis at [G/ C] 10 , [GT/CA] 10 , or [TC/AG] 11 microsatellite alleles. Our data demonstrate that in a wild type genetic background, the major factor influencing microsatellite mutagenesis is the allelic sequence composition.

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SOS Mutator DNA Polymerase IV Functions in Adaptive Mutation and Not Adaptive Amplification

Cited by 270 publications

References 58 publications

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation

Stress responses and genetic variation in bacteria

Escherichia coli DNA polymerase IV contributes to spontaneous mutagenesis at coding sequences but not microsatellite alleles

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