Reassessing the Roles of Oxidative DNA Base Lesion 8-oxoGua and Repair Enzyme OGG1 in Tumorigenesis

Overview

Journal J Biomed Sci

Publisher Biomed Central

Specialty Biology

Date 2024 Dec 31

PMID 39741341

Authors

Jing Wang

Chunshuang Li

Jinling Han

Yaoyao Xue

Xu Zheng

Ruoxi Wang

Zsolt Radak

Yusaku Nakabeppu

Istvan Boldogh

Xueqing Ba

Affiliations

Soon will be listed here.

Abstract

ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome. The accumulation of genomic 8-oxoGua and the dysfunction of OGG1 is readily linked to mutagenesis, and subsequently aging-related diseases and tumorigenesis; however, the direct experimental evidence has long been lacking. Recently, a series of studies have shown that guanine oxidation in the genome has a conservative bias, with the tendency to occur in the regulatory regions, thus, 8-oxoGua is not only a lesion to be repaired, but also an epigenetic modification. In this regard, OGG1 is a specific reader of this base modification. Substrate recognition and/or excision by OGG1 can cause DNA conformation changes, affect chromatin modifications, thereby modulating the transcription of genes involved in a variety of cellular processes, including inflammation, cell proliferation, differentiation, and apoptosis. Thus, in addition to the potential mutagenicity, 8-oxoGua may contribute to tumor development and progression through the altered gene expression stemming from its epigenetic effects.

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