Excision of 8‐oxoguanine from methylated CpG dinucleotides by human 8‐oxoguanine DNA glycosylase

Kasymov, Rustem D.; Grin, Inga R.; Endutkin, Anton V.; Smirnov, S. K.; Ищенко, А. А.; Saparbaev, Murat; Zharkov, Dmitry O.

doi:10.1016/j.febslet.2013.08.008

Cited by 22 publications

(17 citation statements)

References 43 publications

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“…Because of this increased DNA damage and decreased repair, S326C- Ogg1 carriers may have an increased potential for cancer development under oxidative stress by a mechanism such as the one proposed in Figure 4. Our findings stand in contrast to studies showing that the S326C-OGG1 variant has constitutively reduced activity compared to the WT protein (23,28,29). The results of this study do not contradict recent findings that S326C-OGG1 undergoes aggregation in vivo under conditions of oxidative stress (48).…”

Section: Discussioncontrasting

confidence: 99%

“…However, such dimerization has yet to be demonstrated under conditions of physiologically relevant oxidative stress, and thus the mechanism of Cys326 oxidation resulting in loss of activity is still unclear. In contrast, several studies indicate that S326C-OGG1 enzymatic activity is equivalent to that of WT OGG1 (25-27), while others have reported constitutively reduced activity in the variant OGG1 (23,28,29). While the methodologies employed in such studies vary, each used purified enzymes under conditions that may alter the redox status of S326C-OGG1.…”

Section: Introductionmentioning

confidence: 87%

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Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

et al. 2015

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Reactive oxygen species threaten genomic integrity by inducing oxidative DNA damage. One common form of oxidative DNA damage is the mutagenic lesion 8-oxoguanine (8-oxodG). One driver of oxidative stress that can induce 8-oxodG is inflammation, which can be initiated by the cytokine tumor necrosis factor alpha (TNF-α). Oxidative DNA damage is primarily repaired by the base excision repair pathway, initiated by glycosylases targeting specific DNA lesions. 8-oxodG is excised by 8-oxoguanine glycosylase 1 (OGG1). A common Ogg1 allelic variant is S326C-Ogg1, prevalent in Asian and Caucasian populations. S326C-Ogg1 is associated with various forms of cancer, and S326C-OGG1 is inactivated by oxidation. However, whether oxidative stress caused by inflammatory cytokines compromises OGG1 variant repair activity remains unknown. We addressed whether TNF-α causes oxidative stress that both induces DNA damage and inactivates S326C-OGG1 via cysteine 326 oxidation. In mouse embryonic fibroblasts, we found that S326C-OGG1 was inactivated only after exposure to H2O2 or TNF-α. Treatment with the antioxidant N-acetylcysteine prior to oxidative stress rescued S326C-OGG1 activity, demonstrated by in vitro and cellular repair assays. In contrast, S326C-OGG1 activity was unaffected by potassium bromate, which induces oxidative DNA damage without causing oxidative stress, and presumably cysteine oxidation. This study reveals that Cys326 is vulnerable to oxidation that inactivates S326C-OGG1. Physiologically relevant levels of TNF-α simultaneously induce 8-oxodG and inactivate S326C-OGG1. These results suggest a mechanism that could contribute to increased risk of cancer among S326C-Ogg1 homozygous individuals.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

et al. 2015

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“…By adding APE1 and 5 mM MgCl 2 to the reaction mixture, the OGG1 activity for the 5Ј-C:G substrate was increased 6-fold, suggesting that the OGG1 product binding was weaker in the presence of APE1. In contrast to a recent report (54), an adjacent 5-mC:G base pair did not affect the APE1-mediated stimulation of OGG1 (Fig. 5B).…”

Section: C/g-8-oxog/c) B 5ј-t:g (Ie T/g-8-oxog/c) C 5ј-thf:g (Icontrasting

confidence: 99%

“…Critically, G to T transversions occur under oxidative stress conditions in the sequence context of methylated CpG dinucleotides (40), implying formation of unrepaired 8-oxoG at these sites. A recent study also discussed the possibility of reduced repair efficiency of 8-oxoG at the methylated CpG dinucleotide (54). It is also noted that reactive oxygen species-induced G to T transversions have been found in the CpG sequence contexts in carcinoma cells (58).…”

Section: Discussionmentioning

confidence: 99%

Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide

Sassa

Çağlayan

Dyrkheeva

et al. 2014

Journal of Biological Chemistry

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Background: Base excision repair is an important pathway for cytosine demethylation at the CpG dinucleotide for epigenetic control. Results: A deaminated 5-methylcytosine (thymine) and an adjacent oxidized guanine (7,8-dihydro-8-oxoguanine) retard base excision repair of each lesion. Conclusion: Altered in-tandem CpG dinucleotide is a poor substrate for base excision repair. Significance: Oxidized guanine in a CpG dinucleotide interferes with active DNA demethylation.

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“…However, they have suggested that the oxidation of either a single guanine into 8-oxoguanine (8-oxo-G) or 8-oxo-dG or 5-mC into 5-hydroxymethylcytosine (5-hmC), both adjacent to CpG sites, is crucial for the binding of proteins involved in the condensation and inactivation of chromatin (Valinluck et al, 2004) and for the binding of transcription factors to DNA (Zawia et al, 2009). Moreover, the last group and Kasymov et al (2013) reported that the methylation of a cytosine adjacent to an oxidized guanine (8-hydroxy-2'-deoxyguanosine, 8-OHdG) in CpG sites not only synergistically decreases Ogg1 gene expression but also impairs the ability of OGG1 protein to repair the oxidative damage. Finally, ROS might induce sitespecific hypermethylation via the upregulation of DNMT expression or by increasing the formation of DNA methyltransferase (DNMT) complexes (Wu and Ni, 2015).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure

Hernandez-Cortes

Alvarado-Cruz

Solís-Heredia

et al. 2018

Toxicology and Applied Pharmacology

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Methyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and Ogg1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter. In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.

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Excision of 8‐oxoguanine from methylated CpG dinucleotides by human 8‐oxoguanine DNA glycosylase

Cited by 22 publications

References 43 publications

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide

Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure

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