Affinage

OGG1

N-glycosylase/DNA lyase · UniProt O15527

Length
345 aa
Mass
38.8 kDa
Annotated
2026-04-29
100 papers in source corpus 42 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OGG1 is the principal DNA glycosylase/AP lyase responsible for recognizing and excising the mutagenic oxidative lesion 8-oxoguanine (and formamidopyrimidine) from duplex DNA to initiate base excision repair, as demonstrated by enzymatic reconstitution and knockout mouse studies showing massive 8-oxoG accumulation and elevated spontaneous mutation rates in its absence (PMID:9187114, PMID:10725358). The alpha isoform localizes to both nucleus and mitochondrial nucleoids, where its activity is positively regulated by Cdk4 phosphorylation and RECQL4 helicase interaction, and negatively regulated by O-GlcNAcylation, NEDD4L-mediated ubiquitylation at K341, calpain cleavage at a C-terminal PEST sequence, and S-nitrosylation-induced zinc ejection (PMID:15942030, PMID:33203705, PMID:27816939, PMID:33282879, PMID:18294929, PMID:11522631). Beyond canonical repair, OGG1 bound to 8-oxoG in gene promoters acts as a pioneer factor that facilitates loading of transcription factors including NF-κB and phosphorylated SMAD3 to drive inflammatory and fibrotic gene expression programs, and in mitochondria it serves as an aconitase chaperone that suppresses apoptosis independently of its catalytic activity (PMID:28266569, PMID:36651270, PMID:19524665). Loss of OGG1 in macrophages leads to oxidized mitochondrial DNA release, NLRP3 inflammasome activation, and accelerated atherosclerosis, while mitochondrially-targeted OGG1 overexpression suppresses age-associated STING-dependent neuroinflammation (PMID:27384322, PMID:37011700).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    The fundamental question of whether humans possess an 8-oxoG DNA glycosylase was answered when recombinant OGG1 was shown to excise 8-oxoG via bifunctional glycosylase/AP lyase activity and rescue E. coli mutM/mutY mutator phenotypes, establishing OGG1 as the human functional ortholog of bacterial MutM.

    Evidence Recombinant protein expression, in vitro enzymatic assays, and E. coli mutator strain complementation

    PMID:9187114

    Open questions at the time
    • Catalytic mechanism and structural basis of lesion recognition not yet resolved
    • In vivo relevance in mammalian systems not yet demonstrated
  2. 2000 High

    Whether OGG1 is the principal 8-oxoG repair enzyme in vivo was resolved by knockout mice showing 3–7-fold 8-oxoG accumulation in genomic DNA and elevated spontaneous mutation frequencies, while alternative splicing analysis established that alpha-OGG1 is nuclear and beta-OGG1 is mitochondrial, with the alpha isoform being the major cellular 8-oxoG glycosylase.

    Evidence Gene-targeted knockout mice with 8-oxoG quantification and transgenic mutation reporters; immunodepletion from cell extracts; alternative splicing and subcellular fractionation

    PMID:10329432 PMID:10725358 PMID:10775435

    Open questions at the time
    • Regulation of OGG1 activity in chromatin context unknown
    • Mitochondrial isoform functional significance not established
  3. 2001 High

    How OGG1 activity is modulated post-translationally was first addressed when NO was shown to inactivate OGG1 via S-nitrosylation and zinc ejection, and APE1 was found to stimulate OGG1 turnover by displacing it from AP sites, revealing that OGG1 catalytic output is controlled by both inhibitory modifications and cooperative BER handoff.

    Evidence S-nitrosothiol detection and zinc measurement with NO donors; EMSA displacement assays with APE1/OGG1

    PMID:11356334 PMID:11522631

    Open questions at the time
    • Physiological contexts where NO-mediated inhibition is limiting not defined
    • Other post-translational modifications not yet surveyed
  4. 2002 High

    Whether mitochondrial OGG1 has functional significance was demonstrated when conditional targeting of alpha-OGG1 to mitochondria increased mtDNA repair and improved cell survival after oxidative stress, establishing a direct protective role for OGG1 in maintaining mitochondrial genome integrity.

    Evidence MnSOD-MLS fusion construct with tetracycline-regulated expression; mtDNA repair assays; cell viability measurement

    PMID:12244119

    Open questions at the time
    • Endogenous regulation of alpha-OGG1 mitochondrial import not characterized
    • Relative contribution of alpha vs beta isoforms in mitochondria unclear
  5. 2004 High

    How OGG1 is coordinated with MUTYH in the GO repair system was clarified when MUTYH's C-terminal domain was shown to prevent premature OGG1 excision of 8-oxoG opposite adenine, ensuring correct repair order and preventing mutations.

    Evidence In vitro reconstitution with recombinant MUTYH, OGG1, APEX1; C-terminal MUTYH mutant analysis

    PMID:15199168

    Open questions at the time
    • In vivo validation of sequential coordination not performed
    • Whether other factors enforce this order in chromatin unknown
  6. 2005 High

    The first activating kinase for OGG1 was identified when Cdk4-mediated phosphorylation was shown to enhance 8-oxoG incision activity 2.5-fold, while the cancer-associated S326C polymorphism was found to disrupt cell-cycle-dependent nucleolar relocalization, linking OGG1 regulation to the cell cycle.

    Evidence Yeast two-hybrid, in vitro kinase assay, co-immunoprecipitation, incision assay; EGFP-fusion live-cell imaging with cell cycle synchronization

    PMID:15800211 PMID:15942030

    Open questions at the time
    • Cdk4 phosphorylation site on OGG1 not mapped
    • Functional consequence of nucleolar relocalization not established
  7. 2008 High

    Structural insight into lesion recognition came from crystallographic trapping of an 8-oxoG extrusion intermediate, revealing the pathway by which the lesion transits from an exosite to the active site pocket, while proteolytic regulation was established through identification of calpain I cleavage at a C-terminal PEST sequence triggered by oxidative stress.

    Evidence X-ray crystallography of disulfide cross-linked OGG1-DNA complex with photocaged 8-oxoG; protein sequencing of truncation product, co-IP, and calpain inhibitor rescue

    PMID:18294929 PMID:18507380

    Open questions at the time
    • Full kinetic pathway of base extrusion not resolved at atomic level
    • Physiological circumstances governing calpain-mediated OGG1 degradation not defined
  8. 2009 High

    A repair-independent mitochondrial function of OGG1 was uncovered when catalytically dead OGG1 mutants targeted to mitochondria equally prevented oxidant-induced apoptosis by chaperoning mitochondrial aconitase, dissociating OGG1's protective role from its glycosylase activity.

    Evidence Overexpression of WT and catalytic mutant mt-OGG1; co-immunoprecipitation with aconitase; caspase-9 and aconitase activity assays

    PMID:19524665

    Open questions at the time
    • Structural basis of the OGG1–aconitase interaction unknown
    • Whether this chaperone function occurs at endogenous OGG1 levels not tested
  9. 2016 High

    Multiple new regulatory and signaling roles for OGG1 emerged: O-GlcNAcylation was shown to inhibit OGG1 in diabetic hearts; OGG1 was found to recruit TET1 for oxidative stress-induced DNA demethylation; and Ogg1 deficiency was demonstrated to drive NLRP3 inflammasome activation via oxidized mtDNA release, establishing OGG1 as a node connecting DNA damage to innate immune signaling.

    Evidence In vitro O-GlcNAcylation assay with in vivo OGT mutant rescue; co-IP of OGG1–TET1 with bisulfite sequencing; Ogg1−/−Nlrp3−/− double KO bone marrow transplant with cytosolic mtDNA detection

    PMID:27251462 PMID:27384322 PMID:27816939

    Open questions at the time
    • O-GlcNAcylation sites on OGG1 not mapped
    • Whether OGG1–TET1 interaction is direct or indirect unclear
    • Quantitative contribution of mtDNA vs nuclear DNA damage to inflammasome phenotype not dissected
  10. 2017 Medium

    A transcription-regulatory function was identified when OGG1 bound to 8-oxoG in promoter DNA was shown to facilitate NF-κB binding in a position-dependent manner, and nucleosomal context was found to modulate OGG1 access through spontaneous DNA unwrapping.

    Evidence EMSA with 8-oxoG-containing oligonucleotides plus NF-κB; luciferase reporter; in vitro incision on reconstituted nucleosomes with histone tail deletions

    PMID:28266569 PMID:28892740

    Open questions at the time
    • Genome-wide identification of promoters regulated by OGG1-8-oxoG not performed at this stage
    • Chromatin remodelers cooperating with OGG1 in vivo not identified
  11. 2018 High

    Sub-mitochondrial localization of alpha-OGG1 to nucleoids was resolved by super-resolution microscopy, revising the model that alpha-OGG1 is exclusively nuclear; simultaneously, NEDD4L was identified as an E3 ubiquitin ligase that ubiquitylates OGG1 at K341 to inhibit its activity and regulate its stability, and two-state diffusion kinetics on DNA were characterized at single-molecule resolution.

    Evidence Super-resolution imaging with catalytic mutants and mitochondrial network analysis; in vitro ubiquitylation and co-IP in U2OS cells; single-molecule fluorescence microscopy with biophysical modeling

    PMID:29361033 PMID:29848661 PMID:33282879

    Open questions at the time
    • Import pathway for alpha-OGG1 into mitochondria not molecularly defined
    • In vivo significance of NEDD4L-mediated OGG1 ubiquitylation beyond radiation not tested
    • How two-state diffusion relates to lesion recognition efficiency in chromatin unknown
  12. 2020 High

    Multiple advances converged: systematic cysteine mutagenesis assigned distinct cysteines to glycosylase vs lyase vs structural roles; RECQL4 was identified as an acetylation-regulated OGG1 activator; cohesin and mediator subunits (CDK8, MED12) were shown to be required for OGG1 chromatin recruitment upon oxidative stress; and the S326C variant was shown to be specifically inactivated by oxidation of Cys326.

    Evidence Site-directed mutagenesis with enzymatic assays; co-IP and KO cell lines for RECQL4; siRNA screen plus co-IP for cohesin/mediator; in vitro and cellular repair assays for S326C with antioxidant rescue

    PMID:25534136 PMID:32432680 PMID:32710616 PMID:33203705

    Open questions at the time
    • Whether cohesin/mediator-dependent recruitment extends to all genomic contexts unknown
    • RECQL4 acetylation sites mediating OGG1 interaction not fully defined
    • Population-level functional consequence of S326C variant under physiological oxidative conditions not established
  13. 2022 High

    Pharmacological activation of OGG1 was achieved with TH10785, which generates a new β,δ-lyase activity and shifts downstream BER from APE1-dependent to PNKP1-dependent processing, demonstrating that OGG1's catalytic mechanism can be chemically reprogrammed.

    Evidence Structural characterization; 10-fold in vitro activation; mutagenesis of binding residues Phe-319/Gly-42; cellular PNKP1/APE1 dependency assays

    PMID:35737787

    Open questions at the time
    • In vivo therapeutic efficacy of OGG1 activators not demonstrated
    • Whether altered lyase product is mutagenic or toxic at high levels unknown
  14. 2023 High

    OGG1 was established as a bona fide pioneer factor when ChIP-seq/ATAC-seq showed that OGG1 complexed with 8-oxoG in open chromatin recruits phosphorylated SMAD3 to drive fibrotic gene expression, with pharmacological inhibition (TH5487) abrogating fibrosis in vivo, while mitochondrially-targeted OGG1 overexpression was shown to suppress age-associated neuroinflammation via the STING pathway.

    Evidence ChIP-seq, ATAC-seq, co-IP of OGG1–pSMAD3, TH5487 in mouse fibrosis model; transgenic mtOGG1 mouse with STING phosphorylation and cytosolic mtDNA quantification

    PMID:36651270 PMID:37011700

    Open questions at the time
    • Full repertoire of transcription factors recruited by OGG1 pioneer function not cataloged
    • Whether OGG1 pioneer function requires catalytic activity or only 8-oxoG binding not fully resolved
    • Long-term in vivo safety of OGG1 inhibition in fibrosis models not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how OGG1 mitochondrial import is regulated; the complete set of post-translational modifications and their interplay; whether OGG1's transcriptional pioneer function is genome-wide or restricted to specific promoter contexts; and the therapeutic window for OGG1 activators versus inhibitors given its dual repair and signaling roles.
  • No structural model of OGG1 in a nucleosomal complex
  • Mitochondrial import pathway for alpha-OGG1 not molecularly characterized
  • Quantitative model integrating repair and transcriptional functions of OGG1 lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 7 GO:0003677 DNA binding 5 GO:0016829 lyase activity 4 GO:0016787 hydrolase activity 3 GO:0140110 transcription regulator activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 4 GO:0005694 chromosome 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-73894 DNA Repair 9 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-4839726 Chromatin organization 1 R-HSA-5357801 Programmed Cell Death 1
Partners
APEX1CDK4CDK8MUTYHNEDD4LRECQL4SMAD3TET1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human OGG1 (hMMH) encodes a DNA glycosylase/AP lyase that excises 8-hydroxyguanine (8-oxoG) from duplex DNA, and can rescue a spontaneous mutator strain of E. coli lacking mutM and mutY, reducing mutation rate 4-7 fold. Recombinant protein expression in E. coli; glycosylase and AP lyase in vitro assays; complementation of E. coli mutM/mutY mutator strain Cancer research High 9187114
2000 Mmh/Ogg1 gene knockout mice accumulate 8-hydroxyguanine in liver DNA (3-fold at 9 weeks, 7-fold at 14 weeks) and exhibit substantially increased spontaneous mutation frequencies, establishing that Mmh/Ogg1 is the principal in vivo repair enzyme for 8-oxoG. Targeted gene disruption (knockout mouse); biochemical nicking assay on liver extracts; 8-oxoG quantification; transgenic mutation frequency assay (gpt reporter) Proceedings of the National Academy of Sciences of the United States of America High 10725358 11554290 11978483
2000 Human OGG1 gene is localized on chromosome 3p25-26 and encodes two protein forms via alternative splicing: alpha-hOgg1 (nuclear) and beta-hOgg1 (mitochondrial). The alpha isoform is a DNA glycosylase/AP lyase that excises 8-oxoG and Fapy-G from gamma-irradiated DNA. Alternative splicing analysis; subcellular fractionation; in vitro biochemical assays; radiation hybrid mapping Archives of biochemistry and biophysics High 10449904 10775435 11554314
1999 hMMH type 1a protein (alpha-OGG1) is a major enzyme for repair of 8-hydroxyguanine in human cells; immunodepletion of type 1a from whole-cell extracts abolishes most AP lyase activity. Type 1a-specific antibody immunoprecipitation/depletion; in vitro AP lyase activity assay on cell extracts; Western blot Biochemical and biophysical research communications High 10329432 11978483
2001 Nitric oxide (NO) directly inhibits hOgg1 activity by forming S-nitrosothiol adducts on the protein and causing ejection of zinc ions, without altering hOgg1 expression. Immunoprecipitation of hOgg1 from overexpressing cells; cell-free enzymatic activity assays with NO donors; S-nitrosothiol detection; zinc ion measurement Cancer research High 11522631
2001 Alpha-OGG1 is the predominant nuclear isoform, beta-OGG1 is targeted to mitochondria; authentic hOGG1 and hMYH proteins are detected in both mitochondria and nuclei, with intracellular localization regulated by alternative splicing. Subcellular fractionation; Western blotting with isoform-specific antibodies; alternative splicing analysis Progress in nucleic acid research and molecular biology Medium 11554314
2002 Conditional mitochondrial targeting of alpha-hOGG1 (using the MnSOD mitochondrial localization sequence) increases repair of oxidative damage in mitochondrial DNA and improves cellular survival following oxidative stress. Tetracycline-regulated expression vector with MnSOD MLS; Western blot of mitochondrial fractions; enzyme activity assay; mtDNA repair assays; cell viability after oxidative stress The Journal of biological chemistry High 12244119
2002 CSB (Cockayne syndrome group B protein) physically interacts with hOgg1 (His-tagged CSB pulldown; co-localization after gamma-radiation) and contributes to BER of 8-OH-guanine; CSB also maintains hOgg1 expression levels. His-tagged pulldown; co-localization by immunofluorescence; antibody depletion of CSB; EMSA; incision assays; RT-PCR and Western blot for hOgg1 in CSB-null cells DNA repair Medium 12531019
2005 OGG1 is phosphorylated by Cdk4 (serine-threonine kinase), resulting in a 2.5-fold increase in its 8-oxoG/C incision activity; c-Abl tyrosine-phosphorylates OGG1 in vitro without affecting its activity. Both kinases interact with OGG1 in vitro and in vivo. Yeast two-hybrid; protein array; in vitro kinase assay with recombinant proteins; co-immunoprecipitation from cell extracts; in vitro incision assay after phosphorylation Nucleic acids research High 15942030
2005 The hOGG1-Cys326 polymorphic variant shows disrupted cell-cycle-dependent relocalization to nucleoli during S-phase, explained by altered phosphorylation status of the protein. EGFP-hOGG1 live-cell confocal imaging; cell cycle synchronization; Northern blot; comparison of Ser326 vs Cys326 EGFP fusion localization Nucleic acids research Medium 15800211
2005 Cadmium decreases hOGG1 transcription by reducing binding of transcription factor Sp1 to the hOGG1 promoter, leading to impaired 8-oxoG repair and increased mutation frequency. Western blot; RT-PCR; EMSA/ChIP showing reduced Sp1 binding; HPRT mutation assay; overexpression rescue experiment The Journal of biological chemistry Medium 15760895
2006 UVA irradiation causes hOGG1 to relocalize from nucleoplasm to nuclear speckles (nuclear matrix); this relocalization is triggered by ROS (prevented by antioxidants), does not require lesion recognition by hOGG1, and is accompanied by recruitment of APE1 to speckles. Confocal microscopy; biochemical cell fractionation; ROS scavenger treatment; substrate-binding mutants of hOGG1 Journal of cell science High 17148573
2008 OGG1 is a specific substrate of the Ca2+-dependent protease Calpain I; calpain cleaves OGG1 at a PEST sequence in its C-terminus, and OGG1/Calpain I interact by co-immunoprecipitation in human cells. Oxidative stress (H2O2) or cisplatin triggers calpain-mediated OGG1 degradation, which is blocked by the calpain inhibitor calpeptin. Protein sequencing of truncated OGG1; co-immunoprecipitation; cell-based degradation assays with calpain inhibitor; in vitro calpain digestion DNA repair High 18294929
2009 Mitochondrially-targeted alpha-hOGG1 prevents oxidant-induced apoptosis by acting as a chaperone for mitochondrial aconitase independent of its DNA repair activity; OGG1 co-precipitates with mitochondrial aconitase, and repair-deficient OGG1 mutants are equally protective. Overexpression of mt-hOGG1 (WT and catalytic mutants); co-immunoprecipitation with aconitase; caspase-9 activation assay; aconitase activity measurement; shRNA knockdown with apoptosis readout Free radical biology & medicine High 19524665
2010 OGG1 incision activity on 8-oxodG is inhibited in telomeric structures (fork, 3'-overhang, D-loop) compared to duplex DNA, depending on lesion position; TRF1 and TRF2 do not impair OGG1 incision activity on telomeric substrates in vitro. In vitro incision assays on telomeric vs non-telomeric substrates; various DNA structural configurations; OGG1 activity with/without TRF1/TRF2 DNA repair Medium 20951653
2014 The S326C OGG1 variant is inactivated by oxidation of Cys326 induced by H2O2 or TNF-α; N-acetylcysteine pretreatment rescues S326C-OGG1 activity; potassium bromate, which causes DNA damage without cysteine oxidation, does not affect S326C-OGG1 activity. In vitro and cellular repair assays; antioxidant rescue; differential agent treatment; comparison with WT OGG1 DNA repair High 25534136
2015 Small molecule inhibitors of OGG1 (hydrazides/acyl hydrazones) inhibit Schiff base formation during catalysis without reducing OGG1-DNA binding, with >100-fold selectivity over other DNA glycosylases; five inhibitors have IC50 < 1 µM. Fluorescence-based high-throughput screen (~50,000 compounds); multiple biochemical assays for validation; Schiff base trapping assay; DNA binding assay ACS chemical biology High 26218629
2016 OGG1 is essential for oxidative stress-induced DNA demethylation; OGG1 binds 8-oxoG and recruits TET1 to the lesion site, promoting demethylation. Knockdown of OGG1 prevents, and overexpression facilitates, oxidative stress-induced demethylation. Co-immunoprecipitation of OGG1 with TET1; siRNA knockdown and overexpression with demethylation assay; bisulfite sequencing Cellular signalling Medium 27251462
2016 Ogg1-deficient macrophages accumulate oxidized mitochondrial DNA and release more cytosolic mtDNA, leading to increased NLRP3 inflammasome activation and IL-1β secretion; transplantation of Ogg1-/-Nlrp3-/- bone marrow reverses the increased plaque phenotype of Ogg1(-/-) mice. Bone marrow transplantation in Ldlr KO mice; genetic epistasis (Ogg1-/-Nlrp3-/- double KO); IL-1β ELISA; inflammasome activation assays; cytosolic mtDNA detection Circulation research High 27384322
2016 O-GlcNAcylation of Ogg1 in diabetic hearts inhibits its enzymatic activity; reducing O-GlcNAc transferase activity (dominant negative F460A mutant) in vivo restores Ogg1 activity and reduces 8-OHdG and mtDNA damage. In vitro O-GlcNAcylation assay; co-immunoprecipitation; Ogg1 activity assay; dominant negative OGT mutant overexpression in vivo; 8-OHdG measurement The Journal of biological chemistry High 27816939
2017 OGG1 bound to 8-oxoG in promoter DNA facilitates NF-κB binding to cognate DNA targets in a position-dependent manner; OGG1 is essential for NF-κB-dependent gene expression prior to 8-oxoG excision. EMSA with wild-type and 8-oxoG-containing oligonucleotides; nuclear extracts from TNFα-stimulated cells; purified NF-κB; luciferase reporter assay Scientific reports Medium 28266569
2017 hOGG1 activity in nucleosomes is facilitated by spontaneous and transient unwrapping of DNA from histones; activity is suppressed by histone tails, and is position-dependent (inhibited near the dyad axis without chromatin remodelers). In vitro OGG1 incision assays on reconstituted nucleosomes; hydroxyl radical footprinting; histone tail deletion experiments DNA repair High 28892740
2018 The E3 ubiquitin ligase NEDD4L ubiquitylates OGG1 primarily at lysine 341, inhibiting its DNA glycosylase/lyase activity in vitro; NEDD4L and OGG1 interact in U2OS cells, and NEDD4L depletion increases OGG1 stability post-irradiation. Purification of E3 ligase from cell extracts; in vitro ubiquitylation assay; co-immunoprecipitation; OGG1 activity assay; NEDD4L siRNA depletion; cell survival assay Frontiers in cell and developmental biology High 33282879
2018 The alpha-OGG1 isoform, previously considered exclusively nuclear, has a functional mitochondrial-targeting sequence and localizes to mitochondrial nucleoids; its enzymatic activity within mitochondria is required to preserve the mitochondrial network under oxidative stress. Subcellular fractionation; super-resolution microscopy of sub-mitochondrial localization; OGG1 catalytic mutants; mitochondrial network analysis after oxidative stress Journal of cell science High 29848661
2020 RECQL4 helicase physically and functionally interacts with OGG1; RECQL4 promotes OGG1 catalytic activity; acute oxidative stress increases RECQL4 acetylation and its interaction with OGG1; SIRT1 deacetylates RECQL4 in vitro and in cells, thereby negatively regulating the RECQL4-OGG1 interaction. Co-immunoprecipitation; in vitro OGG1 incision assay in presence/absence of RECQL4; RECQL4 KO cells (8-oxoG accumulation); acetylation assay; SIRT1 in vitro deacetylation assay Nucleic acids research High 32432680
2020 hOGG1 searches for 8-oxoG by microscopic 2D and 3D diffusion steps (not simple 1D sliding); strand transfers are limited to distances <7 phosphate linkages, as demonstrated by covalent phosphate roadblock experiments. Single-molecule imaging; molecular clock method; covalent phosphate roadblock assay; numerical simulations Nucleic acids research High 25016526
2020 The cysteines of OGG1 have distinct functional roles: C146 and C255 are necessary for glycosylase activity; C140, C163, C241, and C253 are required for lyase activity; C253 also contributes to structural stability; C28 and C75 have no identified function. Site-directed mutagenesis of each cysteine; in vitro glycosylase and lyase activity assays; structural stability assessment The Journal of biological chemistry High 33203705
2020 OGG1 inhibitor TH5487 binds OGG1's active site, prevents 8-oxoG excision, impairs OGG1 chromatin binding and recruitment to DNA damage sites, resulting in 8-oxoG accumulation and fewer DSBs under oxidative stress. Cell-based OGG1 recruitment assay (live imaging); 8-oxoG immunofluorescence; DSB measurement; chromatin binding assay Biomolecules Medium 33114607
2020 OGG1 depletion in cancer cells causes S-phase DNA damage and replication stress; OGG1 inhibition arrests cancer cell proliferation, validating OGG1 as a cancer target that cooperates with PARP1 in BER. shRNA depletion; OGG1 inhibitor treatment; S-phase DNA damage markers; replication stress assays; in vivo xenograft models Nucleic acids research Medium 33211885
2020 Cohesin and mediator subunits (CDK8, MED12) are required for OGG1 relocalization to chromatin upon oxidative stress; CDK8 and MED12 bind chromatin and interact with OGG1 in response to oxidative stress, enabling efficient 8-oxoG removal. siRNA high-throughput screen; co-immunoprecipitation of OGG1 with mediator/cohesin subunits; chromatin fractionation; 8-oxoG repair assay Nucleic acids research High 32710616
2022 Small molecule TH10785 activates OGG1 10-fold by interacting with residues Phe-319 and Gly-42, generates a new β,δ-lyase enzymatic function, and shifts repair to a PNKP1-dependent rather than APE1-dependent pathway in cells. Structural characterization; in vitro enzymatic activity assay (10-fold activation); mutagenesis of interaction residues; cellular repair assay; PNKP1/APE1 dependency assays Science (New York, N.Y.) High 35737787
2023 OGG1 complexed with 8-oxoG in open chromatin acts as a pioneer factor that recruits phosphorylated SMAD3 to pro-fibrotic gene promoters, driving transcriptional reprogramming in TGFβ1-induced fibrosis; pharmacological inhibition with TH5487 abrogates fibrotic gene expression. ChIP-seq/ATAC-seq for OGG1 and chromatin; co-immunoprecipitation of OGG1 with pSMAD3; TH5487 inhibitor treatment; luciferase reporter and gene expression assays; mouse model of TGFβ1-induced fibrosis Nucleic acids research High 36651270
2023 Mitochondrially-targeted OGG1 (mtOGG1) overexpression reduces age-associated neuroinflammation by decreasing release of mtDNA into the cytoplasm, thereby suppressing STING pathway activation and reducing pro-inflammatory cytokines. Transgenic mtOGG1 mouse model; cytokine/TNFα measurement; STING phosphorylation assay; cytosolic mtDNA quantification; LPS stimulation of HMC3 cells expressing mtOGG1 Free radical biology & medicine Medium 37011700
2001 APEX1/APE1 protein enhances OGG1 AP lyase activity by gel mobility shift displacement (APEX displaces OGG1 from the AP site-containing oligonucleotide complex), and increased APEX expression under oxidative stress augments OGG1-initiated repair. Gel mobility shift assay; in vitro DNA cleavage assay with GST-OGG1 and APEX; RT-PCR and Western blot for expression in HeLa cells Mutation research Medium 11356334
2007 Tuberin (TSC2) regulates OGG1 transcription via the transcription factor NF-YA; NF-YA binding to CAAT boxes in the OGG1 promoter is reduced in tuberin-deficient cells, and TSC2 restoration rescues NF-YA and OGG1 expression. siRNA knockdown and TSC2 cDNA rescue; EMSA and ChIP for NF-YA binding to OGG1 promoter; OGG1 promoter-reporter assay; CAAT box mutagenesis American journal of physiology. Renal physiology Medium 17989114
2010 Tuberin regulates OGG1 transcription through the transcription factor AP4; AP4 co-immunoprecipitates with tuberin, binds the OGG1 promoter by ChIP, and AP4 knockdown decreases OGG1 protein. Co-immunoprecipitation (tuberin/AP4); ChIP for AP4 at OGG1 promoter; siRNA knockdown of AP4; OGG1 promoter reporter; TSC2 rescue Carcinogenesis Medium 20837600
2008 hOGG1 structural intermediates in lesion extrusion have been trapped by X-ray crystallography: a very advanced intermediate shows the 8-oxoG lesion transited from the exosite to the active site pocket without cleavage, revealing the late-stage extrusion pathway. X-ray crystallography of disulfide cross-linked hOGG1-DNA complex with photocaged oxoG; irradiation and flash-freezing to trap intermediate Journal of the American Chemical Society High 18507380
2018 Single-particle trajectory analysis reveals hOGG1 undergoes two-state diffusion kinetics on DNA: switching between a loosely bound, highly mobile state (detachment-competent, pH and salt sensitive) and a tightly bound, less mobile state; the protein spends roughly equal time in each state. Single-molecule fluorescence microscopy; optimal estimator analysis of diffusion trajectories; pH and salt concentration variation Nucleic acids research High 29361033
2004 MUTYH prevents OGG1 from inappropriately excising 8-oxoG opposite adenine (before MUTYH completes A excision) or processing MUTYH's AP-site product, via MUTYH's C-terminal domain; R361A and G365D C-terminal mutants of MUTYH fail to prevent OGG1 activity on these substrates. In vitro incision assays with recombinant MUTYH, OGG1, and APEX1; C-terminal MUTYH mutants; DNA binding affinity (Kd) measurements Nucleic acids research High 15199168

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA. Proceedings of the National Academy of Sciences of the United States of America 564 1495996
2000 The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Archives of biochemistry and biophysics 403 10775435
1995 Functional cooperation of MutT, MutM and MutY proteins in preventing mutations caused by spontaneous oxidation of guanine nucleotide in Escherichia coli. Mutation research 313 7739614
1997 Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue. Cancer research 310 9187114
2000 Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice. Proceedings of the National Academy of Sciences of the United States of America 304 10725358
1991 MutM, a protein that prevents G.C----T.A transversions, is formamidopyrimidine-DNA glycosylase. Nucleic acids research 209 1649454
2005 Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature. Molecular carcinogenesis 204 15584022
2001 Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by nitric oxide. Cancer research 160 11522631
2016 Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis. Circulation research 159 27384322
2003 DNA lesion recognition by the bacterial repair enzyme MutM. The Journal of biological chemistry 152 14525999
2002 Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM. Nature structural biology 151 12055620
2001 Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. International journal of cancer 140 11307145
2001 Regulation of intracellular localization of human MTH1, OGG1, and MYH proteins for repair of oxidative DNA damage. Progress in nucleic acid research and molecular biology 132 11554314
2000 Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. The EMBO journal 127 10921868
2006 Oxidative damage to purines in DNA: role of mammalian Ogg1. DNA repair 112 17127104
2012 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PloS one 109 23284747
2010 Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1. DNA repair 106 20951653
2003 Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways. DNA repair 99 12531387
2007 Identification and characterization of OGG1 mutations in patients with Alzheimer's disease. Nucleic acids research 98 17426120
2002 Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein. DNA repair 87 12531019
2002 Conditional targeting of the DNA repair enzyme hOGG1 into mitochondria. The Journal of biological chemistry 85 12244119
2015 Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1). ACS chemical biology 81 26218629
2016 OGG1 is essential in oxidative stress induced DNA demethylation. Cellular signalling 79 27251462
2005 Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant. Nucleic acids research 79 15800211
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2018 The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. Scientific reports 66 30291284
2009 Role of mitochondrial hOGG1 and aconitase in oxidant-induced lung epithelial cell apoptosis. Free radical biology & medicine 66 19524665
2005 Cadmium down-regulates human OGG1 through suppression of Sp1 activity. The Journal of biological chemistry 65 15760895
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1998 Molecular cloning of AtMMH, an Arabidopsis thaliana ortholog of the Escherichia coli mutM gene, and analysis of functional domains of its product. Molecular & general genetics : MGG 63 9819050
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2016 O-GlcNAcylation of 8-Oxoguanine DNA Glycosylase (Ogg1) Impairs Oxidative Mitochondrial DNA Lesion Repair in Diabetic Hearts. The Journal of biological chemistry 55 27816939
2018 Searching for assay controls for the Fpg- and hOGG1-modified comet assay. Mutagenesis 54 28992346
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2009 Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants. Urology 47 19914697
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2007 A distinct role of formamidopyrimidine DNA glycosylase (MutM) in down-regulation of accumulation of G, C mutations and protection against oxidative stress in mycobacteria. DNA repair 41 17698424
2000 Identification of repair enzymes for 5-formyluracil in DNA. Nth, Nei, and MutM proteins of Escherichia coli. The Journal of biological chemistry 41 10956660
2001 Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer. European journal of cancer (Oxford, England : 1990) 40 11239755
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2015 Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice. Cell reports 39 26711335
2009 Entrapment and structure of an extrahelical guanine attempting to enter the active site of a bacterial DNA glycosylase, MutM. The Journal of biological chemistry 39 19889642
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2007 Increased ROS generation in subsets of OGG1 knockout fibroblast cells. Mechanisms of ageing and development 37 18006041
2014 Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells. DNA repair 35 25534136
2011 XRCC1 and hOGG1 genes and risk of nasopharyngeal carcinoma in North African countries. Molecular carcinogenesis 35 21520294
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1997 The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity. Nucleic acids research 34 9358166
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2020 Interaction between RECQL4 and OGG1 promotes repair of oxidative base lesion 8-oxoG and is regulated by SIRT1 deacetylase. Nucleic acids research 28 32432680
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2013 Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 24186001
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