TY - JOUR
T1 - 8-Oxo-7,8-dihydroguanine
T2 - Links to gene expression, aging, and defense against oxidative stress
AU - Radak, Zsolt
AU - Boldogh, Istvan
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - 8-Oxo-7,8-dihydroguanine
KW - 8-Oxoguanine DNA glycosylase
KW - Aging
KW - Free radicals
KW - Guanine
KW - Hormesis
KW - Oxidative stress
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U2 - 10.1016/j.freeradbiomed.2010.05.008
DO - 10.1016/j.freeradbiomed.2010.05.008
M3 - Article
C2 - 20483371
AN - SCOPUS:77954563673
SN - 0891-5849
VL - 49
SP - 587
EP - 596
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 4
ER -