Impact of reactive oxygen species on spontaneous mutagenesis in <i>Escherichia coli</i>

Sakai, Akiko; Nakanishi, Mari; Yoshiyama, Kaoru; Maki, Hisaji

doi:10.1111/j.1365-2443.2006.00982.x

Cited by 87 publications

(97 citation statements)

References 25 publications

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“…If this is the case, spontaneous recombination events, mostly sister-chromatid exchange, occurring within the target sequence should be much more frequent than those for the allelic recombination in the normally growing wild-type cells. This notion is consistent with a highly frequent generation of spontaneous DNA lesion in aerobically growing E. coli cells (Sakai et al, 2006). In the present study, we found a novel mutator phenotype of a ΔrecA strain.…”

Section: Discussionsupporting

confidence: 77%

“…Since most of the hot-spot type of point mutations in plasmid-born rpsL are likely caused by sequence-substitution mutagenesis (Yoshiyama et al, 2001), such hot-spot mutations could be suppressed in the chromosomal rpsL target sequence by the same reason as the sequence substitutions are suppressed. Recently, we showed that oxidative DNA lesions are involved in mutagenesis for the hot-spot type of base substitutions in the chromosomal rpsL target sequence (Sakai et al, 2006). The reason why the chromosomal hot-spot mutations were not found in the plasmid-born rpsL mutations is unknown.…”

Section: Discussionmentioning

confidence: 99%

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Roles of RecA protein in spontaneous mutagenesis in Escherichia coli

et al. 2007

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To verify the extent of contribution of spontaneous DNA lesions to spontaneous mutagenesis, we have developed a new genetic system to examine simultaneously both forward mutations and recombination events occurring within about 600 base pairs of a transgenic rpsL target sequence located on Escherichia coli chromosome. In a wild-type strain, the recombination events were occurring at a frequency comparable to that of point mutations within the rpsL sequence. When the cells were UV-irradiated, the recombination events were induced much more sharply than point mutations. In a recA null mutant, no recombination event was observed. These data suggest that the blockage of DNA replication, probably caused by spontaneous DNA lesions, occurs often in normally growing E. coli cells and is mainly processed by cellular functions requiring the RecA protein. However, the recA mutant strain showed elevated frequencies of single-base frameshifts and large deletions, implying a novel mutator action of this strain. A similar mutator action of the recA mutant was also observed with a plasmid-based rpsL mutation assay. Therefore, if the recombinogenic problems in DNA replication are not properly processed by the RecA function, these would be a potential source for mutagenesis leading to single-base frameshift and large deletion in E. coli. Furthermore, the single-base frameshifts induced in the recA-deficient cells appeared to be efficiently suppressed by the mutS-dependent mismatch repair system. Thus, it seems likely that the single-base frameshifts are derived from slippage errors that are not directly caused by DNA lesions but made indirectly during some kind of error-prone DNA synthesis in the recA mutant cells.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Roles of RecA protein in spontaneous mutagenesis in Escherichia coli

et al. 2007

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“…Moreover, the mutation rates of wild-type E. coli are typically lower when cells are cultured anaerobically, and the spectrum of mutations shifts away from those that are associated with oxidative stress (86). These data indicate that in aerobic habitats oxidative damage is abundant enough that it is probably the predominant source of DNA damage and mutagenesis.…”

Section: Dna Repairmentioning

confidence: 76%

Cellular Defenses against Superoxide and Hydrogen Peroxide

Imlay

2008

Annu. Rev. Biochem.

1,335

1,310

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Life evolved in an anaerobic world; therefore, fundamental enzymatic mechanisms and biochemical pathways were refined and integrated into metabolism in the absence of any selective pressure to avoid reactivity with oxygen. After photosystem 2 appeared, environmental oxygen levels rose very slowly. During this time microorganisms acquired oxygen tolerance by jettisoning enzymes that use glycyl radicals and low-potential iron-sulfur clusters, which can be directly poisoned by oxygen. They also developed mechanisms to defend themselves against O 2 − and hydrogen peroxide, partially reduced oxygen species that are generated as inadvertent by-products of aerobic metabolism. These species are more chemically reactive than is molecular oxygen itself. Contemporary organisms have inherited both the vulnerabilities and the defenses of these ancestral microbes. Current research seeks to identify these, and bacteria comprise an exceptionally accessible experimental system that has provided the many of the answers. This manuscript reviews recent developments and identifies remaining puzzles.

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“…It has also been observed that the strong mutator phenotypes of cells defective in both the mutM and mutY genes or in the mutT gene are completely suppressed under anaerobic conditions (Sakai et al, 2006).…”

Section: Clinical Implications Of Hypermutator Strainsmentioning

confidence: 97%

Bacterial hypermutation: clinical implications

Jolivet‐Gougeon

Kovács

Gall‐David

et al. 2011

Journal of Medical Microbiology

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Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research. IntroductionEradication of infectious diseases is constantly challenged by micro-organisms that develop new survival strategies. Previous studies suggest that mutational events play a predominant role in bacterial adaptation and confer a selective advantage (Chou et al., 2009;Cooper, 2007). Early experiments aimed at detecting mutators used mutagenized laboratory strains of bacteria, sometimes coupled with different selection strategies. LeClerc et al. (1996) reported high mutation frequency among Escherichia coli and Salmonella pathogens, challenging the theory that mutators were rare among bacterial populations. Taken together, these findings demonstrated that natural populations could respond to environmental selection in two ways, i.e. by enhanced mutation frequencies and by recombination. Transient mutator status, which involves reversion or recombination within the mutator alleles or depletion of the methyl-directed mismatch repair (MMR) system proteins, allows the organism to temporarily benefit from the elevated mutation frequency for adaptation while reducing the risk of accumulating deleterious mutations. Using a mathematical model, Rosche & Foster (1999) showed that transient hypermutators play a role in adaptive mutation in E. coli. Molecular mechanisms of hypermutationProteins involved in the DNA mismatch repair pathway help replace nucleotides introduced erroneously into the replicated DNA and also hinder recombination between non-identical DNA sequences. Deficiencies in any of the DNA mismatch repair pathway mechanisms can lead to a hypermutator phenotype. DNA repairSiegel & Bryson (1967) discovered the mutS gene in an azaserine-resistant derivative of E. coli that had a mutator phenotype and carried a deletion in the mutS gene. The majority of naturally occurring strong mutators have defects in the MMR system; the mutations are mainly in mutS (Oliver et al., 2002), but deletions in genes encoding beta-clamp proteins and in mutH, mutL and mutU (uvrD) have also been described (Fig. 1). Inactivation of basal excision repair genes, e.g. mutY, mutM, ...

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Impact of reactive oxygen species on spontaneous mutagenesis in Escherichia coli

Cited by 87 publications

References 25 publications

Roles of RecA protein in spontaneous mutagenesis in Escherichia coli

Roles of RecA protein in spontaneous mutagenesis in Escherichia coli

Cellular Defenses against Superoxide and Hydrogen Peroxide

Bacterial hypermutation: clinical implications

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