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Towards a comprehensive view of 8-oxo-7,8-dihydro-2’-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability
DNA Repair ( IF 3.0 ) Pub Date : 2020-11-26 , DOI: 10.1016/j.dnarep.2020.103027
Francesca Gorini 1 , Giovanni Scala 2 , Marcus S Cooke 3 , Barbara Majello 2 , Stefano Amente 1
Affiliation  

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.



中文翻译:

全面了解 8-oxo-7,8-diHydro-2'-deoxyguanosine:强调 DNA 损伤和表观遗传学在基因组不稳定性中相互交织的作用

8-oxo-7,8-二氢-2′-脱氧鸟苷 (8-oxodG) 是 DNA 氧化的主要产物,是一种诱变前损伤,如果不修复,很容易在 DNA 过程中与 2′-脱氧腺苷错配。复制。虽然未修复或不完全修复的 8-oxodG 通常与基因组不稳定和癌症相关,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。

尽管越来越多的全基因组 8-oxodG 作图研究已被用来提供关于基因组内 8-oxodG 功能性质的新见解,但将 8-oxodG 的表观遗传和诱变性质结合在一起的全面观点仍然缺乏。

为了帮助弥补这一差距,本综述旨在提供 (i) 关于 8-oxodG 诱变和表观遗传作用的最新知识的描述;(ii) 8-oxodG 可导致基因组不稳定的推定分子模型;(iii) 一个可能的分子模型,说明 8-oxodG 作为表观遗传信号如何引起与癌症相关的易位和缺失。

更新日期:2020-12-04
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