Abstract

The GO system is part of the DNA base excision repair pathway and is required for the error-free repair of 8-oxoguanine (oxoG), one of the most common oxidative DNA lesions. Due to the ability of oxoG to form oxoG:A mispairs, this base is highly mutagenic. Its repair requires the action of two enzymes: 8-oxoguanine DNA glycosylase (Fpg or MutM in bacteria and OGG1 in eukaryotes), which removes oxoG from oxoG:C pairs, and adenine DNA glycosylase (MutY in bacteria and MUTYH in eukaryotes), which removes A from oxoG:A mispairs to prevent mutations. The third enzyme of the system (MutT in bacteria and MTH1 or NUDT1 in eukaryotes) hydrolyzes 8-oxo-2′-deoxyguanosine triphosphate, thus preventing its incorporation into DNA. Recent data point to the proteins of the GO system as promising targets for the therapy of cancer, autoimmune diseases, and bacterial infections. This review highlights the structure and specificity of the GO system in bacteria and eukaryotes and its unique role in mutation avoidance.

中文翻译：

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GO系统，应对氧化损伤的DNA修复途径

摘要

GO系统是DNA碱基切除修复途径的一部分，是8-氧代鸟嘌呤（oxoG）（最常见的氧化性DNA损伤之一）的无差错修复所必需的。由于oxoG形成oxoG：A错配的能力，该碱基高度诱变。其修复需要两种酶的作用：8-氧鸟嘌呤DNA糖基化酶（细菌中为Fpg或MutM，真核生物中为OGG1），其从oxoG：C对中去除oxoG；以及腺嘌呤DNA糖基化酶（细菌中为MutY，真核生物中为MUTYH）。从oxoG中除去A：错配以防止突变。该系统的第三个酶（细菌中的MutT和真核生物中的MTH1或NUDT1）水解8-oxo-2'-脱氧鸟苷三磷酸，从而防止其掺入DNA。最近的数据表明，GO系统的蛋白质可作为治疗癌症，自身免疫性疾病，和细菌感染。这篇综述强调了GO系统在细菌和真核生物中的结构和特异性，以及其在避免突变中的独特作用。