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

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, 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 genotoxic/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, while they do not have shorter lifespan, nor exhibit severe pathological symptoms including tumor formation. In fact they are increasingly resistant to inflammation. Here we address rarely considered significance of 8-oxoG such as its optimal level in the DNA and RNA in a given condition, essentiality for normal cellular physiology, evolutionary role, ability to soften the effects of oxidative stress in DNA, harmful consequences of its repair, as well as its importance in transcriptional initiation and chromatin relaxation.

Nuclear and mitochondrial genome instability induced by senna (Cassia angustifolia Vahl.) aqueous extract in Saccharomyces cerevisiae strains

“…Notably, SAE did not increase the number of Can R mutants of the msh6ogg1 strain. In fact, double inactivation of OGG1 and MSH6 genes had a synergistic effect on spontaneous mutagenesis (Radak and Boldogh, 2010). This may compromise the detection of other base substitutions, as approximately 80% of base substitution events are spontaneous GC to TA transversions in this strain (Ni et al, 1999;Radak and Boldogh, 2010).…”

“…In fact, double inactivation of OGG1 and MSH6 genes had a synergistic effect on spontaneous mutagenesis (Radak and Boldogh, 2010). This may compromise the detection of other base substitutions, as approximately 80% of base substitution events are spontaneous GC to TA transversions in this strain (Ni et al, 1999;Radak and Boldogh, 2010). These results reinforce the notion that SAE-induced DNA damage involves other pre-mutagenic mismatches, likely leading to base pair substitutions such as GC to AT, GC to TA, and AT to GC, independently of 8-oxoG generation (Boiteux et al, 2002).…”

Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells

“…Among the oxidative-damage DNA lesions, 8-oxoG is the most prevalent product of the oxidative attack on DNA. It accumulates in mtDNA with age and in patients suffering from certain types of cancer or neurodegenerative diseases associated with chronic inflammation (reviewed in [38]). This base damage has particular biological relevance because, unless repaired, it induces G:C to T:A transversion mutations with high frequencies [39].…”

Targeted mRNA Oxidation Regulates Sunflower Seed Dormancy Alleviation during Dry After-Ripening

“…Nucleic acids, in particular, are very sensitive to free radicals. Oxidative DNA damage causes mutations, which have been associated with many heritable diseases and aging in mammals (Radak and Boldogh, 2010). RNA can also be oxidized by ROS, particularly by hydroxyl radicals, and RNA has been shown to be much more vulnerable to oxidative damage than DNA (Kong and Lin, 2010).…”