Modulation of OGG1 enzymatic activity by the cellular machinery – have all the boxes been ticked?

IF 3.2 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-11-01 Epub Date: 2025-10-15 DOI:10.1016/j.dnarep.2025.103904

Alice Eddershaw , Natálie Rudolfová , Holly Dawson , Carlos Benítez-Buelga , Maurice Michel

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引用次数: 0

Abstract

8-oxoguanine DNA glycosylase 1 (OGG1) is the key enzyme responsible for identifying and removing 8-oxoguanine (8-oxoG), the most common oxidative lesion in DNA. While its central role in base excision repair (BER) is well established, OGG1 also plays important roles in transcriptional regulation, cell signalling, and inflammation. As its involvement in these pathways is increasingly recognised, a cohesive overview of how OGG1 activity is regulated within the cell is needed. This review summarises the current understanding of OGG1 regulation at multiple levels, through post-translational modifications (PTMs), dynamic protein-protein interactions, and changes in expression levels. We highlight research on the action of reversible PTMs such as phosphorylation, glycosylation, and acetylation, and emphasise the remaining gaps in our knowledge. OGG1 presents a compelling target for small-molecule modulation with potential therapeutic applications in cancer, inflammatory disorders, and age-related diseases. Finally, we discuss how ubiquitination and the circadian rhythm impact overall OGG1 abundance and consider their implications for therapeutic strategies.

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细胞机制对OGG1酶活性的调节——所有的问题都解决了吗？

8-氧鸟嘌呤DNA糖基化酶1 （OGG1）是识别和去除DNA中最常见的氧化损伤8-氧鸟嘌呤（8-oxoG）的关键酶。虽然OGG1在碱基切除修复（BER）中的核心作用已得到证实，但它在转录调节、细胞信号传导和炎症中也发挥着重要作用。随着人们越来越认识到它参与这些途径，需要对细胞内OGG1活性如何调节进行有凝聚力的概述。本文综述了目前对OGG1在多个水平上的调控，包括翻译后修饰（PTMs）、动态蛋白-蛋白相互作用和表达水平的变化。我们重点研究了可逆性PTMs的作用，如磷酸化、糖基化和乙酰化，并强调了我们知识中的剩余空白。OGG1为小分子调控提供了一个令人信服的靶点，在癌症、炎症性疾病和年龄相关疾病中具有潜在的治疗应用。最后，我们讨论了泛素化和昼夜节律如何影响OGG1的总体丰度，并考虑了它们对治疗策略的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.