scholarly journals The Base Excision Repair System of Salmonella enterica serovar Typhimurium Counteracts DNA Damage by Host Nitric Oxide

2009 ◽  
Vol 5 (5) ◽  
pp. e1000451 ◽  
Author(s):  
Anthony R. Richardson ◽  
Khanh C. Soliven ◽  
Margaret E. Castor ◽  
Penelope D. Barnes ◽  
Stephen J. Libby ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Base Excision Repair ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Excision Repair ◽  
Repair System ◽  
Serovar Typhimurium ◽  
Base Excision ◽  
Base Excision Repair System

scholarly journals The Influence of (5′R)- and (5′S)-5′,8-Cyclo-2′-Deoxyadenosine on UDG and hAPE1 Activity. Tandem Lesions are the Base Excision Repair System’s Nightmare

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1303 ◽  
Author(s):  
Karwowski
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Process ◽  
Dna Lesions ◽  
Repair System ◽  
Base Excision ◽  
Base Excision Repair System ◽  
Tandem Lesions ◽  
Ap Site

DNA lesions are formed continuously in each living cell as a result of environmental factors, ionisation radiation, metabolic processes, etc. Most lesions are removed from the genome by the base excision repair system (BER). The activation of the BER protein cascade starts with DNA damage recognition by glycosylases. Uracil-DNA glycosylase (UDG) is one of the most evolutionary preserved glycosylases which remove the frequently occurring 2′-deoxyuridine from single (ss) and double-stranded (ds) oligonucleotides. Conversely, the unique tandem lesions (5′R)- and (5′S)-5′,8-cyclo-2′-deoxyadenosine (cdA) are not suitable substrates for BER machinery and are released from the genome by the nucleotide excision repair (NER) system. However, the cyclopurines appearing in a clustered DNA damage structure can influence the BER process of other lesions like dU. In this article, UDG inhibition by 5′S- and 5′R-cdA is shown and discussed in an experimental and theoretical manner. This phenomenon was observed when a tandem lesion appears in single or double-stranded oligonucleotides next to dU, on its 3′-end side. The cdA shift to the 5′-end side of dU in ss-DNA stops this effect in both cdA diastereomers. Surprisingly, in the case of ds-DNA, 5′S-cdA completely blocks uracil excision by UDG. Conversely, 5′R-cdA allows glycosylase for uracil removal, but the subsequently formed apurinic/apyrimidinic (AP) site is not suitable for human AP-site endonuclease 1 (hAPE1) activity. In conclusion, the appearance of the discussed tandem lesion in the structure of single or double-stranded DNA can stop the entire base repair process at its beginning, which due to UDG and hAPE1 inhibition can lead to mutagenesis. On the other hand, the presented results can cast some light on the UDG or hAPE1 inhibitors being used as a potential treatment.

scholarly journals When UDG and hAPE1 Meet Cyclopurines. How (5′R) and (5′S) 5′,8-Cyclo-2′-deoxyadenosine and 5′,8-Cyclo-2′-deoxyguanosine Affect UDG and hAPE1 Activity?

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5177
Author(s):  
Michał Szewczuk ◽  
Karolina Boguszewska ◽  
Julia Kaźmierczak-Barańska ◽  
Bolesław T. Karwowski
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Lesions ◽  
Repair System ◽  
Cellular Mechanisms ◽  
Uracil Dna Glycosylase ◽  
Base Excision ◽  
Base Excision Repair System ◽  
Synthetic Oligonucleotides ◽  
Ap Site

Ionizing radiation is a factor that seriously damages cellular mechanisms/macromolecules, e.g., by inducing damage in the human genome, such as 5′,8-cyclo-2′-deoxypurines (cdPus). CdPus may become a component of clustered DNA lesions (CDL), which are notably unfavorable for the base excision repair system (BER). In this study, the influence of 5′S and 5′R diastereomers of 5′,8-cyclo-2′-deoxyadenosine (cdA) and 5′,8-cyclo-2′-deoxyguanosine (cdG) on the uracil-DNA glycosylase (UDG) and human AP site endonuclease 1 (hAPE1) activity has been taken under consideration. Synthetic oligonucleotides containing 2′-deoxyuridine (dU) and cdPu were used as a model of single-stranded CDL. The activity of the UDG and hAPE1 enzymes decreased in the presence of RcdG compared to ScdG. Contrary to the above, ScdA reduced enzyme activity more than RcdA. The presented results show the influence of cdPus lesions located within CDL on the activity of the initial stages of BER dependently on their position toward dU. Numerous studies have shown the biological importance of cdPus (e.g., as a risk of carcinogenesis). Due to that, it is important to understand how to recognize and eliminate this type of DNA damage from the genome.

The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells

2017 ◽  
Vol 36 (7) ◽  
pp. 535-540 ◽  
Author(s):  
Piotr Czarny ◽  
Anna Merecz-Sadowska ◽  
Kinga Majchrzak ◽  
Maciej Jabłkowski ◽  
Janusz Szemraj ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Mononuclear Cells ◽  
Excision Repair ◽  
Repair System ◽  
Peripheral Blood Mononuclear ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Blood Mononuclear Cells ◽  
Base Excision ◽  
Base Excision Repair System

DNA base excision repair potentiates the protective effect of Salmonella Pathogenicity Island 2 within macrophages

Microbiology ◽  
2005 ◽  
Vol 151 (2) ◽  
pp. 557-567 ◽  
Author(s):  
Akamol E. Suvarnapunya ◽  
Murry A. Stein
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Pathogenicity Island ◽  
Discrete Systems ◽  
Dna Lesions ◽  
Repair System ◽  
Dna Base Excision Repair ◽  
Base Excision ◽  
Base Excision Repair System ◽  
Reactive Oxidants

Reactive oxidants are a primary weapon of the macrophage antibacterial arsenal. The ability of virulent Salmonella to repair oxidative DNA lesions via the base-excision repair system (BER) enables its survival and replication within the macrophage, but is not required for extracellular growth. Salmonella also inhibits the targeting of oxidant generators to the Salmonella-containing vacuole (SCV) via Salmonella Pathogenicity Island 2 (SPI2). Accordingly, the relative contributions of these two discrete systems to Salmonella resistance to both oxidative mutagenesis and lethality within RAW 264.7 macrophages were investigated. A mutant unable to initiate BER was constructed by deleting all three BER bifunctional glycosylases (Δfpg/nth/nei), and was significantly impaired for early intramacrophage survival. Mutations in various SPI2 effector (sifA and sseEFG) and structural (ssaV) genes were then analysed in the BER mutant background. Loss of SPI2 function alone appeared to increase macrophage-induced mutation. Statistical analyses of the reduced intramacrophage survival of SPI2 mutants and the corresponding SPI2/BER mutants indicated a synergistic interaction between BER and SPI2, suggesting that SPI2 promotes intramacrophage survival by protecting Salmonella DNA from exposure to macrophage oxidants. Furthermore, this protection may involve the SseF and SseG effectors. In contrast, the SifA effector did not seem to play a major role in oxidant protection. It is speculated that Salmonella initially stalls oxidative killing by preserving its genomic integrity through the function of BER, until it can upregulate SPI2 to limit its exposure to macrophage oxidants.

Base excision repair plays an important role in the protection against nitric oxide- and in vivo-induced DNA damage in Trypanosoma brucei

2019 ◽  
Vol 131 ◽  
pp. 59-71 ◽  
Author(s):  
Miriam Yagüe-Capilla ◽  
Daniel García-Caballero ◽  
Fernando Aguilar-Pereyra ◽  
Víctor M. Castillo-Acosta ◽  
Luis M. Ruiz-Pérez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Trypanosoma Brucei ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision

Self-Resistance to an Antitumor Antibiotic: A DNA Glycosylase Triggers the Base-Excision Repair System in Yatakemycin Biosynthesis

2012 ◽  
Vol 124 (42) ◽  
pp. 10684-10688
Author(s):  
Hui Xu ◽  
Wei Huang ◽  
Qing-Li He ◽  
Zhi-Xiong Zhao ◽  
Feng Zhang ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Glycosylase ◽  
Repair System ◽  
Antitumor Antibiotic ◽  
Base Excision ◽  
Base Excision Repair System

scholarly journals The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2857 ◽  
Author(s):  
Karolina Boguszewska ◽  
Michał Szewczuk ◽  
Julia Kaźmierczak-Barańska ◽  
Bolesław T. Karwowski
Keyword(s):  
Base Excision Repair ◽  
Stress Responses ◽  
Excision Repair ◽  
Mitochondrial Diseases ◽  
Premature Aging ◽  
Repair System ◽  
Holistic View ◽  
Atp Production ◽  
Base Excision ◽  
Base Excision Repair System

Mitochondria emerged from bacterial ancestors during endosymbiosis and are crucial for cellular processes such as energy production and homeostasis, stress responses, cell survival, and more. They are the site of aerobic respiration and adenosine triphosphate (ATP) production in eukaryotes. However, oxidative phosphorylation (OXPHOS) is also the source of reactive oxygen species (ROS), which are both important and dangerous for the cell. Human mitochondria contain mitochondrial DNA (mtDNA), and its integrity may be endangered by the action of ROS. Fortunately, human mitochondria have repair mechanisms that allow protecting mtDNA and repairing lesions that may contribute to the occurrence of mutations. Mutagenesis of the mitochondrial genome may manifest in the form of pathological states such as mitochondrial, neurodegenerative, and/or cardiovascular diseases, premature aging, and cancer. The review describes the mitochondrial structure, genome, and the main mitochondrial repair mechanism (base excision repair (BER)) of oxidative lesions in the context of common features between human mitochondria and bacteria. The authors present a holistic view of the similarities of mitochondria and bacteria to show that bacteria may be an interesting experimental model for studying mitochondrial diseases, especially those where the mechanism of DNA repair is impaired.

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