Excision by the human methylpurine DNA<i>N</i>‐glycosylase of cyanuric acid, a stable and mutagenic oxidation product of 8‐oxo‐7,8‐dihydroguanine

Dhérin, Claudine; Gasparutto, Didier; O’Connor, Tim; Cadet, Jean; Boiteux, Serge

doi:10.1080/09553000310001632976

Cited by 15 publications

(7 citation statements)

References 49 publications

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“…Indeed, inflammation‐induced 8‐oxo‐dG levels were elevated in MPG‐deficient mice, substantiating the finding that MPG can excise this lesion . Being highly reactive toward oxidizing reagents, 8‐oxo‐dG can form secondary lesions, such as cyanuric acid, which are further recognized and solely excised by MPG …”

Section: Introductionsupporting

confidence: 64%

“…18 Being highly reactive toward oxidizing reagents, 8-oxo-dG can form secondary lesions, such as cyanuric acid, 23 which are further recognized and solely excised by MPG. 24 Indeed, unlike hOGG1, MPG is able to recognize an extensive array of structurally divergent DNA adducts induced by bile salts. 14 For instance, deamination of adenine by the RNS nitrous anhydride generates hypoxanthine, a promutagenic adduct, which is exclusively recognized and excised by MPG.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic correlation between the expression of the DNA repair enzymeN-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study

et al. 2012

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EAC in its early stages, when it can potentially be cured, is rarely symptomatic and is associated with high mortality rates because in part of late-stage diagnosis. Given that DNA repair is an important contributory factor of early-stage malignancy, our study focused on the expression of the base excision repair enzyme N-methylpurine DNA glycosylase (MPG) in EAC disease onset. MPG messenger RNA (mRNA) expression levels were determined using quantitative reverse transcriptase polymerase chain reaction from a maximum of 72 patient samples. Immunohistochemistry was further utilized for the detection of MPG protein, and semiquantitative analysis performed using an H-score approach was carried out on a total of 130 archival tissue samples of different esophageal pathologies. Nuclear localized MPG protein was detected in all nonmalignant tissues derived from the enterohepatic system, with H-score values of 3.9-5.5 ± 0.4-1.0. In cancerous tissues derived from the enterohepatic system, a 9.5-fold increase in the level of MPG mRNA expression was specifically observed in the malignant regions located within the esophagus region. Further analysis revealed a 9- and 14-fold increase in MPG mRNA expression in EAC tumor, node, metastasis stages II and III, respectively, suggesting MPG expression to correlate with EAC disease progression. Immunohistochemistry analysis further showed a sevenfold significant increase in MPG protein expression in EAC tissues. Intriguingly, there was a fivefold significant decrease in nuclear localized MPG protein expression in tissues derived from Barrett's esophagus and low-grade dysplasia. Such findings highlight a complex regulatory pattern governing DNA glycosylase base excision repair initiation, as normal tissue undergoes Barrett's metaplasia and later dedifferentiates to EAC. Indeed, disease-stage-specific alterations in the expression of MPG may highlight a potential role for MPG in determining EAC onset and thus potentially be of clinical relevance for early disease detection and increased patient survival.

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Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Diagnostic correlation between the expression of the DNA repair enzymeN-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study

et al. 2012

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“…1, N 6 -ethenoadenine) ( 87 , 88 ), deaminated purines (e.g. hypoxanthine, xanthine, oxanine) ( 89 , 90 ), the 8-oxoguanine oxidation product cyanuric acid ( 91 ), uracil ( 86 ) and O -glycosidic additions to deoxyribose ( 21 ). Many of these substrates can be excised from both double-stranded and single-stranded DNA ( 86 , 90 ).…”

Section: Base Damage Repair Pathwaysmentioning

confidence: 99%

The current state of eukaryotic DNA base damage and repair

2015

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DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair.

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“…The 8-oxoG lesion can itself be oxidized to more complex lesions such as spiroiminodihdantoin and cyanuric acid. These lesions are processed by NTH, NEIL 1/2, and MPG (Dherin et al, 2004;Hailer et al, 2005).…”

Section: Dna Glycosylases and Damage Recognitionmentioning

confidence: 99%

Base excision repair, aging and health span

Herzig

Rotrekl

et al. 2008

Mechanisms of Ageing and Development

100

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DNA damage and mutagenesis are suggested to contribute to aging through their ability to mediate cellular dysfunction. The base excision repair (BER) pathway ameliorates a large number of DNA lesions that arise spontaneously. Many of these lesions are reported to increase with age. Oxidized guanine, repaired largely via base excision repair, is particularly well studied and shown to increase with age. Spontaneous mutant frequencies also increase with age which suggests that mutagenesis may contribute to aging. It is widely accepted that genetic instability contributes to age-related occurrences of cancer and potentially other age-related pathologies. BER activity decreases with age in multiple tissues. The specific BER protein that appears to limit activity varies among tissues. DNA polymerase-beta is reduced in brain from aged mice and rats while AP endonuclease is reduced in spermatogenic cells obtained from old mice. The differences in proteins that appear to limit BER activity among tissues may represent true tissue-specific differences in activity or may be due to differences in techniques, environmental conditions or other unidentified differences among the experimental approaches. Much remains to be addressed concerning the potential role of BER in aging and age-related health span.

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Excision by the human methylpurine DNAN‐glycosylase of cyanuric acid, a stable and mutagenic oxidation product of 8‐oxo‐7,8‐dihydroguanine

Cited by 15 publications

References 49 publications

Diagnostic correlation between the expression of the DNA repair enzymeN-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study

Diagnostic correlation between the expression of the DNA repair enzymeN-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study

The current state of eukaryotic DNA base damage and repair

Base excision repair, aging and health span

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