Elsevier

Redox Biology

Volume 14, April 2018, Pages 669-678
Redox Biology

Graphical Review
8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base lesions

https://doi.org/10.1016/j.redox.2017.11.008Get rights and content
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Abstract

Oxidative stress and the resulting damage to genomic DNA are inevitable consequences of endogenous physiological processes, and they are amplified by cellular responses to environmental exposures. One of the most frequent reactions of reactive oxygen species with DNA is the oxidation of guanine to pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG). Despite the vulnerability of guanine to oxidation, vertebrate genes are primarily embedded in GC-rich genomic regions, and over 72% of the promoters of human genes belong to a class with a high GC content. In the promoter, 8-oxoG may serve as an epigenetic mark, and when complexed with the oxidatively inactivated repair enzyme 8-oxoguanine DNA glycosylase 1, provide a platform for the coordination of the initial steps of DNA repair and the assembly of the transcriptional machinery to launch the prompt and preferential expression of redox-regulated genes. Deviations/variations from this artful coordination may be the etiological links between guanine oxidation and various cellular pathologies and diseases during ageing processes.

Graphical abstract

Binding of OGG1 to genomic 8-oxoguanine facilitates gene expression. Proposed actions of OGG1 on open chromatin region (left), OGG1 binding to its substrate facilitates DNA occupancy of transcription factors (NF-κB is shown as example) and promote transcription. If guanine oxidation occurs at closed chromatin region (right), binding of OGG1 could block the interaction of methyl binding proteins (BMPs) with their substrates, subsequently recruit transcription machinery components to activate transcription.

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Abbreviations

ROS
reactive oxygen species
8-oxoG
7, 8-dihydro-8-oxoguanine
OGG1
8-oxoguanine DNA glycosylase 1
BER
base excision repair
OGG1-BER
OGG1-initiated DNA base excision repair
IIR
innate immune response
TNFα
Tumor necrosis factor alpha
NF-κB
Nuclear Factor kappa B
Sp1
specificity protein1
AP-1
activator protein 1
STAT1
signal transducer and activator of transcription 1
(Me)C
methylation of cytosine
MBPs
methyl-CpG-binding proteins

Keywords

OGG1
8-oxoguanine
Gene expression regulation
Epigenetic
DNA methylation

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