α,β-Unsaturated Aldehyde-Induced Delays in Nucleotide Excision Repair and the Contribution of Reactive Oxygen Species

2018 ◽  
Vol 31 (2) ◽  
pp. 145-155 ◽  
Author(s):  
Guang Yang ◽  
Yuko Ibuki
Keyword(s):  
Reactive Oxygen Species ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Unsaturated Aldehyde ◽  
Nucleotide Excision

scholarly journals Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO3-Induced DNA Damage

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Maria A. Spassova ◽  
David J. Miller ◽  
Alexander S. Nikolov
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Dose Response ◽  
Excision Repair ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Repair Processes ◽  
Base Excision

We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemicalKBrO3which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibitsKBrO3-caused oxidative damage. Our modeling revealed that sustained exposure toKBrO3can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical’s toxicity dose dependence based on the dose-response of early genotoxic events.

scholarly journals Role for Nucleotide Excision Repair in Virulence of Mycobacterium tuberculosis

2005 ◽  
Vol 73 (8) ◽  
pp. 4581-4587 ◽  
Author(s):  
K. Heran Darwin ◽  
Carl F. Nathan
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Excision Repair ◽  
Uv Light ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Phagocyte Oxidase ◽  
Nitric Oxide Synthase 2

ABSTRACT Mutations in Mycobacterium tuberculosis uvrB result in severe sensitivity to acidified nitrite, a source of nitric oxide (6). In this study, we show that a uvrB mutant is exquisitely sensitive to UV light but not to several sources of reactive oxygen species in vitro. Furthermore, a uvrB mutant was attenuated in mice as judged by an extension of life span. Attenuation in mice was partially reversed by genetic inactivation of nitric oxide synthase 2 (iNOS) and almost completely reversed in mice lacking both iNOS and phagocyte oxidase. Thus, a gene predicted to encode a key element of DNA repair is required for resistance of M. tuberculosis to both reactive nitrogen and reactive oxygen species in mice.

scholarly journals OGG1 protects mouse spermatogonial stem cells from reactive oxygen species in culture†

2020 ◽  
Author(s):  
Yoshifumi Mori ◽  
Narumi Ogonuki ◽  
Ayumi Hasegawa ◽  
Mito Kanatsu-Shinohara ◽  
Atsuo Ogura ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Excision Repair ◽  
Point Mutations ◽  
Reactive Oxygen ◽  
Functional Screening ◽  
Oxygen Species ◽  
Self Renewal

Abstract Although reactive oxygen species (ROS) are required for spermatogonial stem cell (SSC) self-renewal, they induce DNA damage and are harmful to SSCs. However, little is known about how SSCs protect their genome during self-renewal. Here, we report that Ogg1 is essential for SSC protection against ROS. While cultured SSCs exhibited homologous recombination-based DNA double-strand break repair at levels comparable with those in pluripotent stem cells, they were significantly more resistant to hydrogen peroxide than pluripotent stem cells or mouse embryonic fibroblasts, suggesting that they exhibit high levels of base excision repair (BER) activity. Consistent with this observation, cultured SSCs showed significantly lower levels of point mutations than somatic cells, and showed strong expression of BER-related genes. Functional screening revealed that Ogg1 depletion significantly impairs survival of cultured SSCs upon hydrogen peroxide exposure. Thus, our results suggest increased expression of BER-related genes, including Ogg1, protects SSCs from ROS-induced damage.

scholarly journals Link between Base Excision Repair (BER), Reactive Oxygen Species (ROS), and Cancer

2021 ◽  
Author(s):  
Nour Fayyad ◽  
Farah Kobaisi ◽  
Mohammad Fayyad-Kazan ◽  
Ali Nasrallah ◽  
Hussein Fayyad-Kazan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Base Excision
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