8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification

Abstract

In pathophysiology, reactive oxygen species control diverse cellular phenotypes by oxidizing biomolecules. Among these, the guanine base in nucleic acids is the most vulnerable to producing 8-oxoguanine, which can pair with adenine. Because of this feature, 8-oxoguanine in DNA (8-oxo-dG) induces a G > T (C > A) mutation in cancers, which can be deleterious and thus actively repaired by DNA repair pathways. 8-Oxoguanine in RNA (o(8)G) causes problems in aberrant quality and translational fidelity, thereby it is subjected to the RNA decay pathway. In addition to oxidative damage, 8-oxo-dG serves as an epigenetic modification that affects transcriptional regulatory elements and other epigenetic modifications. With the ability of o(8)G center dot A in base pairing, o(8)G alters structural and functional RNA-RNA interactions, enabling redirection of posttranscriptional regulation. Here, we address the production, regulation, and function of 8-oxo-dG and o(8)G under oxidative stress. Primarily, we focus on the epigenetic and epitranscriptional roles of 8-oxoguanine, which highlights the significance of oxidative modification in redox-mediated control of gene expression. Genetics: modification of guanine base has far-reaching consequences Emerging evidence suggests the modified base 8-oxoguanine, created when damaging chemicals called reactive oxygen species interact with DNA and RNA, has more extensive effects on cell function than previously suspected. This modified form of guanine, one of the key chemical 'bases' of DNA and RNA can cause mutations in DNA and disrupt the functioning of the RNA copies of DNA that mediate gene expression. These problems occur because 8-oxoguanine can aberrantly pair up with the base adenine in crucial DNA and RNA interactions, generating mutations that can cause cancers and other conditions. Sung Wook Chi and colleagues at Korea University in Seoul, review research offering evidence of the wider consequences of 8-oxoguanine formation, especially disruption of the complex processes that regulate the activity of genes and RNA. Further investigation of the medical implications is warranted.