The roles of base excision repair enzyme OGG1 in gene expression

Wang, Ruoxi; Hao, Wenjing; Pan, Lang; Boldogh, István; Ba, Xueqing

doi:10.1007/s00018-018-2887-8

Cited by 75 publications

(65 citation statements)

References 77 publications

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“…Studies by others have also depicted mechanisms by which OGG1 plays key roles in transcriptional modulation of gene expression, where OGG1 functions as a bona fide repair enzyme, and transcription is achieved upon the formation of the strand break or AP site. These observations may suit the regulation of genes downstream of different signaling pathways, or in other types of cells 19,23‐24,60 . Since OGG1 requires reducing cellular conditions for base excision, the pathophysiological contexts of these studies may reflect a post‐ROS‐assault cellular status.…”

Section: Discussionmentioning

confidence: 99%

“…OGG1 oxidative modification at cysteine residues is a reversible modification that can be regained after redox balance is restored 25,33,36,37 . Inactivation of OGG1 via cysteine oxidation does not interfere with genomic substrate binding, but halts its glycosylase activity 3,23,25,33‐34,39 . The vast numbers of OGG1 K249Q analyses help us to comprehend the mechanism of how oxidatively inactivated OGG1 modulates gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…The transcriptional regulation of pro‐inflammatory genes is an important component of innate immune responses, which are associated with changes in cellular redox homeostasis 23,25,70 . Paradoxically, guanine in gene regulatory regions and the repair enzyme OGG1 are targets of ROS.…”

Section: Discussionmentioning

confidence: 99%

“…These facts imply that guanine oxidation may be an approach to modulating gene expression in response to OS. Recently, OGG1's role in transcription regulation has drawn increasing attention 3,14,19,23‐29 . At least two different mechanisms have been proposed: one needs OGG1's glycosylase activity; while the other only requires the binding of OGG1 with the substrate.…”

Section: Introductionmentioning

confidence: 99%

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Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription

et al. 2020

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8‐Oxoguanine DNA glycosylase1 (OGG1)‐initiated base excision repair (BER) is the primary pathway to remove the pre‐mutagenic 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) from DNA. Recent studies documented 8‐oxoG serves as an epigenetic‐like mark and OGG1 modulates gene expression in oxidatively stressed cells. For this new role of OGG1, two distinct mechanisms have been proposed: one is coupled to base excision, while the other only requires substrate binding of OGG1––both resulting in conformational adjustment in the adjacent DNA sequences providing access for transcription factors to their cis‐elements. The present study aimed to examine if BER activity of OGG1 is required for pro‐inflammatory gene expression. To this end, Ogg1/OGG1 knockout/depleted cells were transfected with constructs expressing wild‐type (wt) and repair‐deficient mutants of OGG1. OGG1's promoter enrichment, oxidative state, and gene expression were examined. Results showed that TNFα exposure increased levels of oxidatively modified cysteine(s) of wt OGG1 without impairing its association with promoter and facilitated gene expression. The excision deficient K249Q mutant was even a more potent activator of gene expression; whereas, mutant OGG1 with impaired substrate recognition/binding was not. These data suggested the interaction of OGG1 with its substrate at regulatory regions followed by conformational adjustment in the adjacent DNA is the primary mode to modulate inflammatory gene expression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription

et al. 2020

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“…The long-standing view is that 8-oxoG is mutagenic and detrimental to cellular processes such as gene transcription. However, there is increasing evidence that in addition to being a pre-mutagenic DNA lesion, 8-oxoG also plays an essential role in the regulation of gene expression along with the DNA repair protein OGG1 (Wang et al 2018).…”

Section: Discussionmentioning

confidence: 99%

8-OxoG in GC-rich Sp1 binding sites enhances gene transcription during adipose tissue development in juvenile mice

et al. 2019

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The oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only premutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)-and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.adipose tissue -had GC-rich promoters as compared to those that were moderately active or inactive genes. Furthermore, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as demonstrated by Sp1and ERE-luciferase assays in HEK293T cells under oxidative stress condition. These results suggest that 8-oxoG promotes transcription during adipose tissue development in mice.

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Mechanistic understanding of cellular responses to genomic stress

Hanawalt

Sweasy

2019

Environ and Mol Mutagen

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Within the past half century we have learned of multiple pathways for repairing damaged DNA, based upon the intrinsic redundancy of information in its complementary double strands. Mechanistic details of these pathways have provided insights into environmental and endogenous threats to genomic stability. Studies on bacterial responses to ultraviolet light led to the discovery of excision repair, as well as the inducible SOS response to DNA damage. Similar responses in eukaryotes promote upregulation of error‐prone translesion DNA polymerases. Recent advances in this burgeoning field include duplex DNA sequencing to provide strikingly accurate profiling of mutational signatures, analyses of gene expression patterns in single cells, CRISPR/Cas9 to generate changes at precise genomic positions, novel roles for RNA in gene expression and DNA repair, phase‐separated aqueous environments for specialized cellular transactions, and DNA lesions as epigenetic signals for gene expression. The Environmental Mutagenesis and Genomics Society (EMGS), through the broad range of expertise in its membership, stands at the crossroad of basic understanding of mechanisms for genomic maintenance and the field of genetic toxicology, with the need for regulation of exposures to toxic substances. Our future challenges include devising strategies and technologies to identify individuals who are susceptible to specific genomic stresses, along with basic research on the underlying mechanisms of cellular stress responses that promote disease‐causing mutations. As the science moves forward it should also be a responsibility for the EMGS to expand its outreach programs for the enlightenment and benefit of all humans and the biosphere. Environ. Mol. Mutagen. 61:25–33, 2020. © 2019 Wiley Periodicals, Inc.

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The roles of base excision repair enzyme OGG1 in gene expression

Cited by 75 publications

References 77 publications

Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription

Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription

8-OxoG in GC-rich Sp1 binding sites enhances gene transcription during adipose tissue development in juvenile mice

Mechanistic understanding of cellular responses to genomic stress

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