The dinB Gene Encodes a Novel E. coli DNA Polymerase, DNA Pol IV, Involved in Mutagenesis

Wagner, Jérôme; Grúz, Petr; Kim, Su-Ryang; Yamada, Masami; Matsui, Kazuaki; Fuchs, Robert P. P.; Nohmi, Takehiko

doi:10.1016/s1097-2765(00)80376-7

Cited by 443 publications

(416 citation statements)

References 21 publications

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“…coli polymerase IV is a distributive polymerase that lacks a 3'to 5' exonuclease (proofreading) activity and is prone to elongation of misaligned primer/template structures [20]. The overespression of the polymerase causes -1 frameshifts in polypurine runs of G in undamaged DNA [22].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…The E. coli dinB gene encodes DNA Polymerase IV (Pol IV) [20]. Pol IV does not require recA, umuDC, uvrA, polA or polB for activity [21,22] and errors made by Pol IV are correctable by MMR, suggesting Pol IV contributes to replication errors on undamaged templates [21].…”

Section: Introductionmentioning

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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“…Many of these polymerases can replicate damaged DNA, but this ability comes at the cost of frequent mutations on both damaged and undamaged templates. E. coli has two Y-family DNA polymerases, Pol IV, the product of the dinB gene (also called dinP) [6], and Pol V, the product of the umuDC operon [7][8][9]. Both polymerases are repressed by LexA and induced as part of the SOS response [10][11][12].…”

Section: The Sos Responsementioning

confidence: 99%

Stress responses and genetic variation in bacteria

Foster

2005

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

176

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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“…Single-stranded DNA produced by several DNA-damaging agents and repair mechanisms can be bound by RecA protein, resulting in conversion of this protein to its activated form. Once activated, RecA interacts with LexA protein, the repressor of the SOS genes (Wagner et al, 1999). This interaction triggers the autocatalytic cleavage of LexA and consequent destruction of its ability to function as a repressor, which results in the derepression of SOS genes (Mustard and Little, 2000;Fernandez De Henestrosa et al, 2000).…”

Section: Sos Responsementioning

confidence: 99%

Several pathways of hydrogen peroxide action that damage the E. coli genome

Asad

Almeida

et al. 2004

Genet. Mol. Biol.

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Hydrogen peroxide is an important reactive oxygen species (ROS) that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER), nucleotide excision repair (NER) and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm) and H 2 O 2 , the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H 2 O 2 under low-iron conditions. Key words: hydrogen peroxide, cross-adaptive response, lethal synergism, copper and iron. General AspectsThe appearance of aerobic forms of life was an important step in the evolutionary process, since oxygen consumption leads to the production of ten-fold more energy from glucose than does anaerobic metabolism (Meneghini, 1987). However, this process imposes constraints on cell viability, because of the generation of reactive oxygen species during respiration.The consecutive univalent reduction of molecular oxygen to water produces three active intermediates: superoxide anion (O 2 -• ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH • ). These intermediates, collectively referred to as reactive oxygen species (ROS) are potent oxidants of lipids, proteins, and nucleic acids (Halliwell and Gutteridge, 1984;Mello-Filho and Meneghini, 1985;Meneghini, 1988). Among the oxidative DNA lesions, one of the major classes of DNA damage leads to modification in purine and pyrimidine bases, together with oligonucleotide strand breaks, DNA-protein cross-links and abasic sites. Increasing evidence suggests that the cumulative damage caused by ROS contributes to numerous degenerative diseases associated with aging, such as atherosclerosis, rheumatoid arthritis and cancer (Ames et al., 1993;Halliwell and Gutteridge, 1999).Living organisms have developed specific mechanisms to prevent the production and effects of ROS. The reduction of O 2 by cytochrome oxidase without yielding ROS, the superoxide dismutase catalysis of O 2 -• into H 2 O 2 through a dismutation reaction, the decomposition of H 2 O 2 by catalase and peroxidases, and the scavenging of ROS by some vitamins comprise part of the set of cellular antioxidant defenses (Halliwell and Gutteridge, 1999). Synthesis of the enzymes that catalyze these reactions is a part of the adaptive response tr...

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The dinB Gene Encodes a Novel E. coli DNA Polymerase, DNA Pol IV, Involved in Mutagenesis

Cited by 443 publications

References 21 publications

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

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

Stress responses and genetic variation in bacteria

Several pathways of hydrogen peroxide action that damage the E. coli genome

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