Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
Department of Biology, University of Naples 'Federico II', Naples, Italy.
DNA Repair (Amst). 2021 Jan;97:103027. doi: 10.1016/j.dnarep.2020.103027. Epub 2020 Nov 26.
8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a major product of DNA oxidation, is a pre-mutagenic lesion which is prone to mispair, if left unrepaired, with 2'-deoxyadenosine during DNA replication. While unrepaired or incompletely repaired 8-oxodG has classically been associated with genome instability and cancer, it has recently been reported to have a role in the epigenetic regulation of gene expression. Despite the growing collection of genome-wide 8-oxodG mapping studies that have been used to provide new insight on the functional nature of 8-oxodG within the genome, a comprehensive view that brings together the epigenetic and the mutagenic nature of the 8-oxodG is still lacking. To help address this gap, this review aims to provide (i) a description of the state-of-the-art knowledge on both the mutagenic and epigenetic roles of 8-oxodG; (ii) putative molecular models through which the 8-oxodG can cause genome instability; (iii) a possible molecular model on how 8-oxodG, acting as an epigenetic signal, could cause the translocations and deletions which are associated with cancer.
8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代-dG）是 DNA 氧化的主要产物，是一种潜在的诱变损伤，如果在 DNA 复制过程中未被修复或不完全修复，它很容易与 2'-脱氧腺苷发生错配。虽然未修复或不完全修复的 8-氧代-dG 通常与基因组不稳定性和癌症有关，但最近有报道称它在基因表达的表观遗传调控中发挥作用。尽管已经进行了大量的全基因组 8-氧代-dG 图谱研究，这些研究为了解 8-氧代-dG 在基因组中的功能性质提供了新的见解，但对于 8-氧代-dG 的表观遗传和诱变性质的综合观点仍然缺乏。为了帮助解决这一差距，本综述旨在提供：(i) 对 8-氧代-dG 的诱变和表观遗传作用的最新知识的描述；(ii) 8-氧代-dG 可能导致基因组不稳定性的假设分子模型；(iii) 一个可能的分子模型，说明 8-氧代-dG 如何作为一种表观遗传信号，导致与癌症相关的易位和缺失。
