Contribution of the Mismatch DNA Repair System to the Generation of Stationary-Phase-Induced Mutants of
            <i>Bacillus subtilis</i>

Pedraza-Reyes, Mario; Yasbin, Ronald E.

doi:10.1128/jb.186.19.6485-6491.2004

Cited by 39 publications

(64 citation statements)

References 36 publications

(65 reference statements)

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“…In agreement with this idea, it has been shown that the genetic inactivation of the mismatch (MMR) and guanine-oxidized (GO) systems potentiates the mutagenic events that occur in nongrowing B. subtilis cells (6,7). Thus, it appears that the accumulation of mismatched and oxidized DNA bases in nongrowing B. subtilis cells is a key factor that promotes mutations under conditions of nutritional or metabolic stress (6,7).…”

mentioning

confidence: 55%

“…Three parallel cultures were used to determine the total number of CFU plated onto each plate (N t ) by titration. The mutation rates were calculated as previously described using the following formula: mutation rate ϭ m/2N t (1,6).…”

Section: Methodsmentioning

confidence: 99%

“…It has been proposed that during periods of environmental stress, such as those occurring in the stationary phase of growth, a group of cells in a B. subtilis culture can be differentiated into a subpopulation with suppressed DNA repair systems in which adaptive mutations may be generated (1,6). In agreement with this idea, it has been shown that the genetic inactivation of the mismatch (MMR) and guanine-oxidized (GO) systems potentiates the mutagenic events that occur in nongrowing B. subtilis cells (6,7).…”

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confidence: 99%

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Error-Prone Processing of Apurinic/Apyrimidinic (AP) Sites by PolX Underlies a Novel Mechanism That Promotes Adaptive Mutagenesis in Bacillus subtilis

et al. 2014

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cIn growing cells, apurinic/apyrimidinic (AP) sites generated spontaneously or resulting from the enzymatic elimination of oxidized bases must be processed by AP endonucleases before they compromise cell integrity. Here, we investigated how AP sites and the processing of these noncoding lesions by the AP endonucleases Nfo, ExoA, and Nth contribute to the production of mutations (hisC952, metB5, and leuC427) in starved cells of the Bacillus subtilis YB955 strain. Interestingly, cells from this strain that were deficient for Nfo, ExoA, and Nth accumulated a greater amount of AP sites in the stationary phase than during exponential growth. Moreover, under growth-limiting conditions, the triple nfo exoA nth knockout strain significantly increased the amounts of adaptive his, met, and leu revertants produced by the B. subtilis YB955 parental strain. Of note, the number of stationary-phase-associated reversions in the his, met, and leu alleles produced by the nfo exoA nth strain was significantly decreased following disruption of polX. In contrast, during growth, the reversion rates in the three alleles tested were significantly increased in cells of the nfo exoA nth knockout strain deficient for polymerase X (PolX). Therefore, we postulate that adaptive mutations in B. subtilis can be generated through a novel mechanism mediated by error-prone processing of AP sites accumulated in the stationary phase by the PolX DNA polymerase.

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confidence: 55%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Error-Prone Processing of Apurinic/Apyrimidinic (AP) Sites by PolX Underlies a Novel Mechanism That Promotes Adaptive Mutagenesis in Bacillus subtilis

et al. 2014

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“…General and specific DNA repair systems, mismatch repair, and oxidative damage repair (GO system) have been shown to be repressed or inefficient in cells under conditions of stress in eukaryotic and bacterial systems (19,25,28,45) while errorprone polymerases are active in stationary-phase cells (11,12,19,42,43). Thus, one can speculate that the combination of transcriptional derepression and DNA repair inadequacies under conditions of nongrowth biases mutations to transcribed regions.…”

Section: Resultsmentioning

confidence: 99%

Transcription-Associated Mutation in Bacillus subtilis Cells under Stress

et al. 2010

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Adaptive (stationary phase) mutagenesis is a phenomenon by which nondividing cells acquire beneficial mutations as a response to stress. Although the generation of adaptive mutations is essentially stochastic, genetic factors are involved in this phenomenon. We examined how defects in a transcriptional factor, previously reported to alter the acquisition of adaptive mutations, affected mutation levels in a gene under selection. The acquisition of mutations was directly correlated to the level of transcription of a defective leuC allele placed under selection. To further examine the correlation between transcription and adaptive mutation, we placed a point-mutated allele, leuC427, under the control of an inducible promoter and assayed the level of reversion to leucine prototrophy under conditions of leucine starvation. Our results demonstrate that the level of Leu ؉ reversions increased significantly in parallel with the induced increase in transcription levels. This mutagenic response was not observed under conditions of exponential growth. Since transcription is a ubiquitous biological process, transcription-associated mutagenesis may influence evolutionary processes in all organisms.The generation of mutations has been traditionally ascribed to spontaneous processes affecting actively growing, dividing cells. Nevertheless, by the mid-1950s, several reports describing mutagenesis in nondividing cells of bacteria, plants, flies, and fungi appeared in the scientific literature (reference 36 and references therein). Much of the initial characterization of this process in bacteria took place in the laboratory of Francis Ryan, who observed Escherichia coli mutants capable of synthesizing histidine arising from his mutant (auxotrophic) cells undergoing prolonged starvation (36) while cell turnover remained undetectable, and DNA replication slowed with increasing time (26). Renewed interest in adaptive mutation was generated when Cairns and coworkers published their work on the generation of Lac ϩ reversions in E. coli cells unable to use the lactose provided as the sole carbon source in a minimal medium (6). This work demonstrated that adaptive mutations can arise as a result of stress rather than from selection of preexisting mutations. The generation of stress-induced Lac ϩ reversions, assayed via a plasmid-borne system, has been studied intensively by several laboratories (reviewed in references 13, 15, and 34; 32) and is dependent on activation of the SOS and/or stress responses. Further studies have also suggested that a subpopulation within the Lac Ϫ stressed cells engage in an exquisitely regulated transient state of hypermutation limited in time and to DNA sites near double-stranded DNA breaks (reviewed in reference 15). Collectively, the results from studies on this system have provided interesting insights into the acquisition of beneficial mutations and demonstrated the role of several genetic factors in the adaptive mutation phenomenon.

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“…In addition to direct epigenetic silencing of DNA repair pathways, their inactivation may follow persistent suppression of genes involved in cell cycle control (like APC gene and p53), because these genes mediate DNA repair in mammalian cells. A loss or a decrease of the efficiency of DNA repair and a related increase in the rate of adaptive mutations in the bacterial stationary phase is also well documented [70,[98][99][100][101]. A recent study of adaptive mutagenesis in E. coli showed that the bacterial generalstress-response sigma factor RpoS may control a switch between a high-fidelity DNA repair and an error-prone repair in the case of double-strand breaks [102].…”

Section: Decreased Efficiency Of Dna Repairmentioning

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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Contribution of the Mismatch DNA Repair System to the Generation of Stationary-Phase-Induced Mutants of Bacillus subtilis

Cited by 39 publications

References 36 publications

Error-Prone Processing of Apurinic/Apyrimidinic (AP) Sites by PolX Underlies a Novel Mechanism That Promotes Adaptive Mutagenesis in Bacillus subtilis

Error-Prone Processing of Apurinic/Apyrimidinic (AP) Sites by PolX Underlies a Novel Mechanism That Promotes Adaptive Mutagenesis in Bacillus subtilis

Transcription-Associated Mutation in Bacillus subtilis Cells under Stress

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

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