Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis

Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis

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...

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Bibliographic Details
Main Authors: Jing Wang, Chunshuang Li, Jinling Han, Yaoyao Xue, Xu Zheng, Ruoxi Wang, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Journal of Biomedical Science
Subjects:
8-oxoguanine
OGG1
Epigenetic regulation
Gene expression
Tumorigenesis
Online Access:https://doi.org/10.1186/s12929-024-01093-8
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Summary: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.
ISSN:1423-0127

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