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. 2010 Aug 15;49(4):587-96.
doi: 10.1016/j.freeradbiomed.2010.05.008. Epub 2010 May 17.

8-Oxo-7,8-dihydroguanine: links to gene expression, aging, and defense against oxidative stress

Zsolt Radak  1 , Istvan Boldogh
Affiliations

8-Oxo-7,8-dihydroguanine: links to gene expression, aging, and defense against oxidative stress

Zsolt Radak et al. Free Radic Biol Med. .

Abstract

The one-electron oxidation product of guanine, 8-oxo-7,8-dihydroguanine (8-oxoG), is an abundant lesion in genomic, mitochondrial, and telomeric DNA and RNA. It is considered to be a marker of oxidative stress that preferentially accumulates at the 5' end of guanine strings in the DNA helix, in guanine quadruplexes, and in RNA molecules. 8-OxoG has a lower oxidation potential compared to guanine; thus it is susceptible to oxidation/reduction and, along with its redox products, is traditionally considered to be a major mutagenic DNA base lesion. It does not change the architecture of the DNA double helix and it is specifically recognized and excised by 8-oxoguanine DNA glycosylase (OGG1) during the DNA base excision repair pathway. OGG1 null animals accumulate excess levels of 8-oxoG in their genome, yet they do not have shorter life span nor do they exhibit severe pathological symptoms including tumor formation. In fact they are increasingly resistant to inflammation. Here we address the rarely considered significance of 8-oxoG, such as its optimal levels in DNA and RNA under a given condition, essentiality for normal cellular physiology, evolutionary role, and ability to soften the effects of oxidative stress in DNA, and the harmful consequences of its repair, as well as its importance in transcriptional initiation and chromatin relaxation.

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Figures

Figure 1
Figure 1. A hypothetical role of oxidized guanines in cellular processes
Oxidation of guanine in the DNA helix could result in the replacement of cytosine by thymine, and this could cause a mutation (arrow 1). Due to its low redox potential guanine attracts reactive species; in the telomere quaduplexes and RNA it could thus be a potential buffer in preventing further oxidative damage to DNA helix-located guanines (arrow 2). Moderate levels of guanine oxidation could be important to an open chromatin structure, which is an obligatory process for transcription (arrow 3).
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