scholarly journals Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis in Escherichia coli

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6029 ◽  
Author(s):  
Caroline Zutterling ◽  
Aibek Mursalimov ◽  
Ibtissam Talhaoui ◽  
Zhanat Koshenov ◽  
Zhiger Akishev ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Dna Repair ◽  
Uv Irradiation ◽  
Genome Stability ◽  
Dna Duplexes ◽  
E Coli ◽  
Dna Strands ◽  
Induced Mutagenesis

Background DNA repair is essential to counteract damage to DNA induced by endo- and exogenous factors, to maintain genome stability. However, challenges to the faithful discrimination between damaged and non-damaged DNA strands do exist, such as mismatched pairs between two regular bases resulting from spontaneous deamination of 5-methylcytosine or DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved the mismatch-specific DNA glycosylases that can recognize and remove regular DNA bases in the mismatched DNA duplexes. The Escherichia coli adenine-DNA glycosylase (MutY/MicA) protects cells against oxidative stress-induced mutagenesis by removing adenine which is mispaired with 7,8-dihydro-8-oxoguanine (8oxoG) in the base excision repair pathway. However, MutY does not discriminate between template and newly synthesized DNA strands. Therefore the ability to remove A from 8oxoG•A mispair, which is generated via misincorporation of an 8-oxo-2′-deoxyguanosine-5′-triphosphate precursor during DNA replication and in which A is the template base, can induce A•T→C•G transversions. Furthermore, it has been demonstrated that human MUTYH, homologous to the bacterial MutY, might be involved in the aberrant processing of ultraviolet (UV) induced DNA damage. Methods Here, we investigated the role of MutY in UV-induced mutagenesis in E. coli. MutY was probed on DNA duplexes containing cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproduct (6–4PP). UV irradiation of E. coli induces Save Our Souls (SOS) response characterized by increased production of DNA repair enzymes and mutagenesis. To study the role of MutY in vivo, the mutation frequencies to rifampicin-resistant (RifR) after UV irradiation of wild type and mutant E. coli strains were measured. Results We demonstrated that MutY does not excise Adenine when it is paired with CPD and 6–4PP adducts in duplex DNA. At the same time, MutY excises Adenine in A•G and A•8oxoG mispairs. Interestingly, E. coli mutY strains, which have elevated spontaneous mutation rate, exhibited low mutational induction after UV exposure as compared to MutY-proficient strains. However, sequence analysis of RifR mutants revealed that the frequencies of C→T transitions dramatically increased after UV irradiation in both MutY-proficient and -deficient E. coli strains. Discussion These findings indicate that the bacterial MutY is not involved in the aberrant DNA repair of UV-induced DNA damage.

scholarly journals The antimutagenic effect of monoterpenes against UV-irradiation-, 4NQO- and t-BOOH-induced mutagenesis in coli

2011 ◽  
Vol 63 (1) ◽  
pp. 117-128 ◽  
Author(s):  
Biljana Nikolic ◽  
Dragana Mitic-Culafic ◽  
Branka Vukovic-Gacic ◽  
Jelena Knezevic-Vukcevic
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Uv Irradiation ◽  
Mutagenic Effect ◽  
Evolutionary Conservation ◽  
Induced Mutations ◽  
Mutagenic Potential ◽  
E Coli ◽  
Antimutagenic Effect ◽  
Induced Mutagenesis

The aim of this work was to investigate the antimutagenic potential of monoterpenes from sage and basil in Escherichia coli. The mutagenic potential of monoterpenes was pre-screened with Salmonella/microsome reversion assay in strain TA100 and no mutagenic effect was detected. The antimutagenic potential against UV- 4NQO- and t-BOOH induced mutagenesis was evaluated in E. coli K12 and E. coli WP2 by reversion assays. The obtained results indicate that camphor and thujone reduce UV- and 4NQO-induced mutations; myrcene reduces t-BOOH-induced mutations, while eucalyptol and linalool reduce mutagenicity by all tested mutagens. Considering evolutionary conservation of DNA repair and antioxidative protection, the obtained results indicate that further antigenotoxicity studies should be undertaken in eukaryotes.

Mutagenesis and More: umuDC and the Escherichia coli SOS Response

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1599-1610 ◽  
Author(s):  
Bradley T Smith ◽  
Graham C Walker
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Cellular Response ◽  
Sos Response ◽  
Posttranslational Regulation ◽  
E Coli ◽  
Sos Mutagenesis ◽  
Induced Mutagenesis ◽  
Mechanistic Basis ◽  
Increase Cell Survival

Abstract The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and posttranslational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.

scholarly journals The Role of Posttranslational Modifications in DNA Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Protein Localization ◽  
Complex Structure ◽  
Protein Protein Interactions ◽  
Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

Involvement of the cgtA gene function in stimulation of DNA repair in Escherichia coli and Vibrio harveyi

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1763-1770 ◽  
Author(s):  
Ryszard Zielke ◽  
Aleksandra Sikora ◽  
Rafał Dutkiewicz ◽  
Grzegorz Wegrzyn ◽  
Agata Czyż
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Repair ◽  
Gene Product ◽  
Uv Irradiation ◽  
Vibrio Harveyi ◽  
Bacterial Species ◽  
Wild Type ◽  
E Coli ◽  
Stimulation Of

CgtA is a member of the Obg/Gtp1 subfamily of small GTP-binding proteins. CgtA homologues have been found in various prokaryotic and eukaryotic organisms, ranging from bacteria to humans. Nevertheless, despite the fact that cgtA is an essential gene in most bacterial species, its function in the regulation of cellular processes is largely unknown. Here it has been demonstrated that in two bacterial species, Escherichia coli and Vibrio harveyi, the cgtA gene product enhances survival of cells after UV irradiation. Expression of the cgtA gene was found to be enhanced after UV irradiation of both E. coli and V. harveyi. Moderate overexpression of cgtA resulted in higher UV resistance of E. coli wild-type and dnaQ strains, but not in uvrA, uvrB, umuC and recA mutant hosts. Overexpression of the E. coli recA gene in the V. harveyi cgtA mutant, which is very sensitive to UV light, restored the level of survival of UV-irradiated cells to the levels observed for wild-type bacteria. Moreover, the basal level of the RecA protein was lower in a temperature-sensitive cgtA mutant of E. coli than in the cgtA + strain, and contrary to wild-type bacteria, no significant increase in recA gene expression was observed after UV irradiation of this cgtA mutant. Finally, stimulation of uvrB gene transcription under these conditions was impaired in the V. harveyi cgtA mutant. All these results strongly suggest that the cgtA gene product is involved in DNA repair processes, most probably by stimulation of recA gene expression and resultant activation of RecA-dependent DNA repair pathways.

scholarly journals The Virulence Plasmid-Encoded impCAB Operon Enhances Survival and Induced Mutagenesis in Shigella flexneriafter Exposure to UV Radiation

1999 ◽  
Vol 67 (3) ◽  
pp. 1415-1423 ◽  
Author(s):  
Laura J. Runyen-Janecky ◽  
Mei Hong ◽  
Shelley M. Payne
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Nucleotide Sequence ◽  
Uv Radiation ◽  
Uv Irradiation ◽  
Shigella Flexneri ◽  
Virulence Plasmid ◽  
Repair System ◽  
Induced Mutagenesis ◽  
Dna Fragment

ABSTRACT Upon exposure to UV radiation, Shigella flexneri SA100 displayed survival and mutation frequencies comparable to those ofEscherichia coli AB1157, which contains a functional UmuDC error-prone DNA repair system. Survival of SA100 after UV irradiation was associated with the presence of the 220-kb virulence plasmid, pVP. This plasmid encodes homologues of ImpA and ImpB, which comprise an error-prone DNA repair system encoded on plasmid TP110 that was initially identified in Salmonella typhimurium, and ImpC, encoded upstream of ImpA and ImpB. Although the impBgene was present in representatives of all four species ofShigella, not all isolates tested contained the gene.Shigella isolates that lacked impB were more sensitive to UV radiation than isolates that containedimpB. The nucleotide sequence of a 2.4-kb DNA fragment containing the imp operon from S. flexneri SA100 pVP was 96% identical to the impoperon from the plasmid TP110. An SA100 derivative with a mutation in the impB gene had reduced survival following UV irradiation and less UV-induced mutagenesis relative to the parental strain. We also found that S. flexneri contained a chromosomally encoded umuDC operon; however, theumuDC promoter was not induced by exposure to UV radiation. This suggests that the imp operon but not theumuDC operon contributes to survival and induced mutagenesis in S. flexneri following exposure to UV radiation.

scholarly journals N6-Methyladenosine, DNA Repair, and Genome Stability

2021 ◽  
Vol 8 ◽  
Author(s):  
Fei Qu ◽  
Pawlos S. Tsegay ◽  
Yuan Liu
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cellular Response ◽  
Genome Stability ◽  
Fine Tuning ◽  
Genome Integrity ◽  
Cell Renewal ◽  
The Novel ◽  
Cellular Sensitivity

N6-methyladenosine (m6A) modification in mRNAs and non-coding RNAs is a newly identified epitranscriptomic mark. It provides a fine-tuning of gene expression to serve as a cellular response to endogenous and exogenous stimuli. m6A is involved in regulating genes in multiple cellular pathways and functions, including circadian rhythm, cell renewal, differentiation, neurogenesis, immunity, among others. Disruption of m6A regulation is associated with cancer, obesity, and immune diseases. Recent studies have shown that m6A can be induced by oxidative stress and DNA damage to regulate DNA repair. Also, deficiency of the m6A eraser, fat mass obesity-associated protein (FTO) can increase cellular sensitivity to genotoxicants. These findings shed light on the novel roles of m6A in modulating DNA repair and genome integrity and stability through responding to DNA damage. In this mini-review, we discuss recent progress in the understanding of a unique role of m6As in mRNAs, lncRNAs, and microRNAs in DNA damage response and regulation of DNA repair and genome integrity and instability.

scholarly journals Role of Deubiquitinating Enzymes in DNA Repair

2015 ◽  
Vol 36 (4) ◽  
pp. 524-544 ◽  
Author(s):  
Younghoon Kee ◽  
Tony T Huang
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Regulatory Mechanisms ◽  
Deubiquitinating Enzymes ◽  
Genome Maintenance ◽  
Dna Damage Signaling ◽  
Damage Response

Both proteolytic and nonproteolytic functions of ubiquitination are essential regulatory mechanisms for promoting DNA repair and the DNA damage response in mammalian cells. Deubiquitinating enzymes (DUBs) have emerged as key players in the maintenance of genome stability. In this minireview, we discuss the recent findings on human DUBs that participate in genome maintenance, with a focus on the role of DUBs in the modulation of DNA repair and DNA damage signaling.

scholarly journals Colibactin-Producing Escherichia coli Induce the Formation of Invasive Carcinomas in a Chronic Inflammation-Associated Mouse Model

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2060
Author(s):  
Laurène Salesse ◽  
Cécily Lucas ◽  
My Hanh Thi Hoang ◽  
Pierre Sauvanet ◽  
Alexandra Rezard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Mouse Model ◽  
Genetic Susceptibility ◽  
Colorectal Carcinogenesis ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Invasive Carcinomas ◽  
Damage Marker

Background: Escherichia coli producing the genotoxin colibactin (CoPEC or colibactin-producing E. coli) abnormally colonize the colonic mucosa of colorectal cancer (CRC) patients. We previously showed that deficiency of autophagy in intestinal epithelial cells (IECs) enhances CoPEC-induced colorectal carcinogenesis in ApcMin/+ mice. Here, we tested if CoPEC trigger tumorigenesis in a mouse model lacking genetic susceptibility or the use of carcinogen. Methods: Mice with autophagy deficiency in IECs (Atg16l1∆IEC) or wild-type mice (Atg16l1flox/flox) were infected with the CoPEC 11G5 strain or the mutant 11G5∆clbQ incapable of producing colibactin and subjected to 12 cycles of DSS treatment to induce chronic colitis. Mouse colons were used for histological assessment, immunohistochemical and immunoblot analyses for DNA damage marker. Results: 11G5 or 11G5∆clbQ infection increased clinical and histological inflammation scores, and these were further enhanced by IEC-specific autophagy deficiency. 11G5 infection, but not 11G5∆clbQ infection, triggered the formation of invasive carcinomas, and this was further increased by autophagy deficiency. The increase in invasive carcinomas was correlated with enhanced DNA damage and independent of inflammation. Conclusions: CoPEC induce colorectal carcinogenesis in a CRC mouse model lacking genetic susceptibility and carcinogen. This work highlights the role of (i) CoPEC as a driver of CRC development, and (ii) autophagy in inhibiting the carcinogenic properties of CoPEC.

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

2004 ◽  
Vol 186 (19) ◽  
pp. 6485-6491 ◽  
Author(s):  
Mario Pedraza-Reyes ◽  
Ronald E. Yasbin
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Bacillus Subtilis ◽  
Stationary Phase ◽  
Assay System ◽  
Repair System ◽  
Induced Mutants ◽  
Induced Mutagenesis ◽  
Mmr Deficiency

ABSTRACT A reversion assay system previously implemented to demonstrate the existence of adaptive or stationary-phase-induced mutagenesis in Bacillus subtilis was utilized in this report to study the influence of the mismatch DNA repair (MMR) system on this type of mutagenesis. Results revealed that a strain deficient in MutSL showed a significant propensity to generate increased numbers of stationary-phase-induced revertants. These results suggest that absence or depression of MMR is an important factor in the mutagenesis of nongrowing B. subtilis cells because of the role of MMR in repairing DNA damage. In agreement with this suggestion, a significant decrease in the number of adaptive revertant colonies, for the three markers tested, occurred in B. subtilis cells which overexpressed a component of the MMR system. Interestingly, the single overexpression of mutS, but not of mutL, was sufficient to decrease the level of adaptive mutants in the reversion assay system of B. subtilis. The results presented in this work, as well as in our previous studies, appear to suggest that an MMR deficiency, putatively attributable to inactivation or saturation with DNA damage of MutS, may occur in a subset of B. subtilis cells that differentiate into the hypermutable state.

Histone marks: repairing DNA breaks within the context of chromatin

2012 ◽  
Vol 40 (2) ◽  
pp. 370-376 ◽  
Author(s):  
Kyle M. Miller ◽  
Stephen P. Jackson
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genome Stability ◽  
Nuclear Dna ◽  
Dna Lesions ◽  
Dna Breaks ◽  
Strand Breaks ◽  
Dna Dsbs

Inherited or acquired defects in detecting, signalling or repairing DNA damage are associated with various human pathologies, including immunodeficiencies, neurodegenerative diseases and various forms of cancer. Nuclear DNA is packaged into chromatin and therefore the true in vivo substrate of damaged DNA occurs within the context of chromatin. Our work aims to decipher the mechanisms by which cells detect DNA damage and signal its presence to the DNA-repair and cell-cycle machineries. In particular, much of our work has focused on DNA DSBs (double-strand breaks) that are generated by ionizing radiation and radiomimetic chemicals, and which can also arise when the DNA replication apparatus encounters other DNA lesions. In the present review, we describe some of our recent work, as well as the work of other laboratories, that has identified new chromatin proteins that mediate DSB responses, control SDB processing or modulate chromatin structure at DNA-damage sites. We also aim to survey several recent advances in the field that have contributed to our understanding of how particular histone modifications and involved in DNA repair. It is our hope that by understanding the role of chromatin and its modifications in promoting DNA repair and genome stability, this knowledge will provide opportunities for developing novel classes of drugs to treat human diseases, including cancer.

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