DNA polymerase II as a fidelity factor in chromosomal DNA synthesis in <i>Escherichia coli</i>

Banach-Orlowska, Magdalena; Fijałkowska, Iwona J.; Schaaper, Roel M.; Jonczyk, Piotr

doi:10.1111/j.1365-2958.2005.04805.x

Cited by 67 publications

(98 citation statements)

References 60 publications

(101 reference statements)

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“…15 DNA polymerases Pol II, Pol IV and Pol V serve as accessory enzymes. [16][17][18] The primary function for Pol II is remains unclear, but it has been suggested that Pol II may serve as a backup enzyme for Pol III 16 and re-initiates DNA synthesis in UV-irradiated E. coli cells. 19 Like Pol III and Pol I, Pol II is considered a high fidelity enzyme due to its proofreading exonuclease activity.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

Gawel¹,

Seed²

2011

Virulence

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Section: Resultsmentioning

confidence: 99%

“…3,4 In some circumstances UPEC rapidly replicates in intracellular bacterial communities (IBC), a biofilm-like state observed in animal and human infections. 3,5 UPEC may also chronically persist in the epithelium (16).…”

Section: Introductionmentioning

confidence: 99%

Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

Gawel¹,

Seed²

2011

Virulence

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“…We used alleles of DNA Pol IV (DinB) ( Table 3) and the dnaE915 allele (21,22), an antimutator allele that reduces DinB-dependent mutations (23,24). Thus, we hypothesized that genetic interactions between dnaE915 and dinB variants should result in detectable changes in DinB-dependent phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Pol III␣(915) is an antimutator either because it synthesizes DNA slower than the native replicative DNA polymerase active subunit, DNA Pol III␣ (21,22), or because it might inhibit low-fidelity DNA synthesis by TLS DNA polymerases, specifically DinB (23). Its antimutator activity is also dependent upon another TLS DNA polymerase, DNA Pol II, which likely prevents mutagenesis generated by DinB (24). This genetic system has permitted us to discover key DinB residues that mapped to specific areas of DinB, allowing us to gain insights into the mechanisms underlying the DinB-mediated overproduction loss-of-survival phenotype.…”

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confidence: 99%

Selection of dinB Alleles Suppressing Survival Loss upon dinB Overexpression in Escherichia coli

et al. 2014

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Escherichia coli strains overproducing DinB undergo survival loss; however, the mechanisms regulating this phenotype are poorly understood. Here we report a genetic selection revealing DinB residues essential to effect this loss-of-survival phenotype. The selection uses strains carrying both an antimutator allele of DNA polymerase III (Pol III) ␣-subunit (dnaE915) and either chromosomal or plasmid-borne dinB alleles. We hypothesized that dnaE915 cells would respond to DinB overproduction differently from dnaE ؉ cells because the dnaE915 allele is known to have an altered genetic interaction with dinB ؉ compared to its interaction with dnaE ؉ . Notably, we observe a loss-of-survival phenotype in dnaE915 strains with either a chromosomal catalytically inactive dinB(D103N) allele or a low-copy-number plasmid-borne dinB ؉ upon DNA damage treatment. Furthermore, we find that the loss-of-survival phenotype occurs independently of DNA damage treatment in a dnaE915 strain expressing the catalytically inactive dinB(D103N) allele from a low-copy-number plasmid. The selective pressure imposed resulted in suppressor mutations that eliminated growth defects. The dinB intragenic mutations examined were either base pair substitutions or those that we inferred to be loss of function (i.e., deletions and insertions). Further analyses of selected novel dinB alleles, generated by single-base-pair substitutions in the dnaE915 strain, indicated that these no longer effect loss of survival upon overproduction in dnaE ؉ strains. These mutations are mapped to specific areas of DinB; this permits us to gain insights into the mechanisms underlying the DinB-mediated overproduction loss-of-survival phenotype.A ll cells accumulate DNA damage that, if left unrepaired, will stall DNA replication due to the inability of high-fidelity DNA polymerases (Pol) to use lesion-containing DNA as templates, a potentially lethal event (1). To ensure survival, Escherichia coli responds to replication fork stalling by upregulating the expression of the SOS-regulated genes (1-3), among which are specialized low-fidelity DNA polymerase genes. These polymerases can perform translesion synthesis (TLS), consisting of both insertion opposite to and elongation from DNA lesions on the template strand (4). TLS can result in elevated mutagenesis. In fact, data suggest that mutations responsible for resistance to several classes of antibiotics require TLS DNA polymerases (5-8). Moreover, these DNA polymerases appear to play a role in the development of disorders such as cancer in metazoans (9-12).E. coli strains lacking the dinB gene (⌬dinB), encoding DinB (DNA Pol IV), one of the TLS DNA polymerases, are sensitive to nitrofurazone (NFZ) and 4-nitroquinoline-1-oxide (4-NQO) (13-15), reagents that generate persistent DNA lesions on the N 2 group of deoxyguanine (N 2 -dG), as well as alkylating agents such as methyl methanesulfonate (MMS) (14,16). Moreover, strains overproducing DinB undergo survival loss. It has been proposed that this is the result of lethal double-s...

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“…E. coli has five DNA polymerases. Pol I, Pol II and Pol III have essentially higher fidelity than Y-family polymerases Pol IV and Pol V. The high fidelity DNA polymerases play an important role in normal DNA replication and in SOS-induced DNA repair [116,137,138]. Although error-prone Pol IV is also involved in the DNA repair activated by SOS response, several studies also suggest that Pol IV functions in implementation of the mutator phenotype.…”

Section: Y Family Polymerasesmentioning

confidence: 99%

Bacterial Stationary-State Mutagenesis and Mammalian Tumorigenesis as Stress-Induced Cellular Adaptations and the Role of Epigenetics

Karpinets

Greenwood²,

Pogribny³

et al. 2006

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Mechanisms of cellular adaptation may have some commonalities across different organisms. Revealing these common mechanisms may provide insight in the organismal level of adaptation and suggest solutions to important problems related to the adaptation. An increased rate of mutations, referred as the mutator phenotype, and beneficial nature of these mutations are common features of the bacterial stationary-state mutagenesis and of the tumorigenic transformations in mammalian cells. We argue that these commonalities of mammalian and bacterial cells result from their stressinduced adaptation that may be described in terms of a common model. Specifically, in both organisms the mutator phenotype is activated in a subpopulation of proliferating stressed cells as a strategy to survival. This strategy is an alternative to other survival strategies, such as senescence and programmed cell death, which are also activated in the stressed cells by different subpopulations. Sustained stress-related proliferative signalling and epigenetic mechanisms play a decisive role in the choice of the mutator phenotype survival strategy in the cells. They reprogram cellular functions by epigenetic silencing of cell-cycle inhibitors, DNA repair, programmed cell death, and by activation of repetitive DNA elements. This reprogramming leads to the mutator phenotype that is implemented by error-prone cell divisions with the involvement of Y family polymerases. Studies supporting the proposed model of stress-induced cellular adaptation are discussed. Cellular mechanisms involved in the bacterial stress-induced adaptation are considered in more detail.

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DNA polymerase II as a fidelity factor in chromosomal DNA synthesis in Escherichia coli

Cited by 67 publications

References 60 publications

Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

Selection of dinB Alleles Suppressing Survival Loss upon dinB Overexpression in Escherichia coli

Bacterial Stationary-State Mutagenesis and Mammalian Tumorigenesis as Stress-Induced Cellular Adaptations and the Role of Epigenetics

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