Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase

Yudkina, Anna V.; Shilkin, Evgeniy S.; Endutkin, Anton V.; Makarova, Аlena V.; Zharkov, Dmitry O.

doi:10.3390/cryst9050269

Cited by 31 publications

(28 citation statements)

References 268 publications

(445 reference statements)

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“…Second, the decreased selectivity for repairing 8-oxoG:A lesions compared with 8-oxoG:C lesions prevents the accumulation of guanine-to-thymine transversion mutations. If the 8-oxoG:A lesion is to be repaired by OGG1, then the polymerase will incorporate a thymine opposite adenine ( 39 , 40 , 41 , 42 ). Thus, it is important for OGG1 to maintain its binding specificity under conditions of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

The role of cysteines in the structure and function of OGG1

Wang

Maayah

Sweasy

et al. 2021

Journal of Biological Chemistry

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8-oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241 and C253), (3) structural stability (C253), and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.

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Section: Discussionmentioning

confidence: 99%

The role of cysteines in the structure and function of OGG1

Wang

Maayah

Sweasy

et al. 2021

Journal of Biological Chemistry

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“…This lesion results in a G-C to T-A transversion. Formed when guanine comes into contact with peroxynitrite or a hydroxyl radical, 8-oxo2dG is a strong mutagen, the severity of whose effects likely depends on the nucleic acid environment, in which it is formed (Isobe et al, 2010;Gmitterová et al, 2018;Yudkina et al, 2019). It seems that the presence of 8-oxo2dG in nucleic acids during replication may lead to somatic mutations and loss of genes' functions in up to 14% of events, followed by a production of nonfunctional proteins, including aberrant DNA repair enzymes (Yasui et al, 2014).…”

Section: Biomarkers Of Oxidative Damagementioning

confidence: 99%

“…When the sanitization of oxidized (d)NTPs by hMTH1 or their excision by the glycosylases OGG1 and MUTYH fail to prevent the occurrence of DNA lesions precursive to transversion mutations upon subsequent replication, DNA polymerases represent the final defense against oxidative damage. Nonetheless, disparities exist between how different polymerases cope with the recognition and removal of oxidized dNTPs (Eoff et al, 2010;Yudkina et al, 2019).…”

Section: Parkinson's Diseasementioning

confidence: 99%

Mitochondrial and Nuclear DNA Oxidative Damage in Physiological and Pathological Aging

Kowalska

Piekut

Prendecki

et al. 2020

DNA and Cell Biology

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Mitochondria play an important role in numerous processes, including energy generation, regulating ion homeostasis, and cell signaling. Mitochondria are also the main source of reactive oxygen species (ROS). Due to the oxidative environment within mitochondria, the macromolecules therein, for example, mtDNA, proteins, and lipids are more susceptible to sustaining damage. During aging, mitochondrial functions decline, partly as a result of an accumulation of mtDNA mutations, decreased mtDNA copy number and protein expression, and a reduction in oxidative capacity. The aim of this study was to summarize the knowledge on DNA oxidative damage in aging and age-related neurodegenerative diseases. It has been hypothesized that various ROS may play an important role not only in physiological senescence but also in the development of neurodegenerative diseases, for example, Alzheimer's disease and Parkinson's disease. Thus, mitochondria seem to be a potential target of novel treatments for neurodegenerative diseases.

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“…When DNA is exposed to oxidative stresses, damages occur in the bases and sugar of some sensitive nucleotides like guanine and lead to forming the side-products such as 8-oxoguanine (8-oxoG) 72 . The 8-oxoG displays mutagenic potential by inducing GC-TA transversion in the DNA replication 73 . Some DNA repairing mechanisms including MMR, BER and NER pathways generally implicate in response to ROS/RNS-induced DNA damages 74 .…”

Section: Studies Have Shown That the Overexpression Of Crys In Numeromentioning

confidence: 99%

Human Cryptochrome Mediates Oxidative Stress Responses Modulated by Static and Electromagnetic Fields in Doxorubicin-Treated Cells

Hajipour-Verdom

Alipour

Abdolmaleki

et al. 2020

Preprint

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Cryptochromes (CRYs) have been suggested to involve in the magnetic sensing for navigation of migratory birds in response to Earth’s magnetic fields. Magnetic fields (MFs) through wireless penetration change the cell physiology by effect on physicochemical reactions. Here, we aimed to investigate the behavior of HEK 293T cells overexpressing human CRY-based magnetoreception complexes undergo doxorubicin (DOX) treatment and exposure to moderate intensity static magnetic field (SMF) and extremely low frequency-pulsed electromagnetic field (ELF-PEMF). The ability of this magnetosensor is depended on CRY-photoreceptor proteins that complemented with putative magnetosensor proteins (MagR). The results indicate that magnetic sensitivity of CRY-based magnetosensor can effects on the intracellular reactive oxygen species (ROS) production and cell growth, cell cycle progression and expression of DNA damage-related genes due to treatment of DOX, SMF and ELF-PEMF. Our findings show that ROS accumulation significantly decreased in the cells expressing CRY/MagR complexes in response to all treatments, and also cell viability is decreased in contrast to MFs exposure. In addition, magnetosensitive complexes mediated the upregulation of genes in the base excision repair (BER) pathway including ITPA in presence of SMF as well as MTH1 in presence of ELF-PEMF in the DOX treated-cells. Furthermore, CRY/MagR induced a remarkable cell cycle arrest at G0/G1 phase in the all treatments. These results demonstrated that CRY/MagR complexes modify the DNA damage responses during genotoxic stresses by controlling the cell cycle progression and ROS levels. Therefore, our data suggest that CRY-based magnetosensitive complexes can increase the cytotoxic effects of DOX even when SMF and/or ELF-PEMF exposure were provided, exclusively.

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Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase

Cited by 31 publications

References 268 publications

The role of cysteines in the structure and function of OGG1

The role of cysteines in the structure and function of OGG1

Mitochondrial and Nuclear DNA Oxidative Damage in Physiological and Pathological Aging

Human Cryptochrome Mediates Oxidative Stress Responses Modulated by Static and Electromagnetic Fields in Doxorubicin-Treated Cells

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