Affinage

OGG1

N-glycosylase/DNA lyase · UniProt O15527

Length
345 aa
Mass
38.8 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OGG1 is the principal cellular DNA glycosylase that initiates base excision repair (BER) of the mutagenic oxidized base 8-oxoguanine, recognizing and excising 8-oxoG with strong preference from 8-oxoG:C base pairs in duplex DNA (PMID:9223305, PMID:9187114, PMID:10329432, PMID:11978483). It is a bifunctional enzyme combining N-glycosylase/AP-lyase activity with a deoxyribophosphodiesterase activity that processes incised AP sites to leave a one-nucleotide gap, and systematic cysteine mutagenesis defines distinct residues required for glycosylase (C146, C255) versus lyase (C140, C163, C241, C253) chemistry (PMID:9358166, PMID:33203705). To locate lesions, OGG1 searches DNA through combined sliding and strand-transfer (hopping) movements (PMID:25016526). Alternative splicing generates a nuclear α-isoform and a mitochondrial β-isoform, and the α-isoform itself carries a functional mitochondrial-targeting signal, associating with mtDNA nucleoids where its catalytic activity preserves the mitochondrial network and limits oxidative damage (PMID:10775435, PMID:11554314, PMID:12244119, PMID:29848661). Beyond canonical repair, substrate-bound but catalytically uncommitted OGG1 functions as a pioneer-like factor at gene regulatory regions: binding to 8-oxoG—rather than excision—enhances NF-κB DNA occupancy and inflammatory gene expression, recruits TET1 to drive oxidative demethylation, and recruits phosphorylated SMAD3 to pro-fibrotic promoters (PMID:27251462, PMID:28266569, PMID:32378256, PMID:36651270). OGG1 activity and abundance are regulated by interacting partners including the RECQL4 helicase (stimulatory, under SIRT1/deacetylation control), cohesin/Mediator subunits required for chromatin recruitment, the CSB protein within a larger complex, and the NEDD4L E3 ligase that targets OGG1 for proteasomal degradation (PMID:12531019, PMID:32432680, PMID:32710616, PMID:35654123). OGG1-initiated repair has double-edged consequences: under excessive oxidative stress the strand breaks and AP sites it generates hyperactivate PARP1 and drive parthanatos, and small-molecule modulators exploit this biology—inhibitors (TH5487) that block substrate binding suppress repair and inflammatory/fibrotic signaling, while the activator TH10785 binds F319/G42 to confer a novel β,δ-lyase activity that reroutes repair to an APE1-independent, PNKP1-dependent pathway (PMID:29795387, PMID:35737787, PMID:36651270, PMID:33114607).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1997 High

    Established the core identity of OGG1 as the enzyme that excises the mutagenic oxidized base 8-oxoguanine, answering what protein initiates repair of this lesion in human cells.

    Evidence Expression of hOGG1 in fpg-deficient E. coli and complementation of the yeast ogg1 mutator phenotype with substrate-specificity assays

    PMID:9187114 PMID:9223305

    Open questions at the time
    • Did not resolve subcellular distribution between nucleus and mitochondria
    • Catalytic residues and mechanism not yet mapped
  2. 1997 High

    Defined how OGG1 hands off to downstream BER by showing it possesses a dRpase activity that processes incised AP sites to a directly fillable gap, clarifying the enzymatic completeness of OGG1-initiated repair.

    Evidence In vitro dRpase assays with purified GST-Ogg1 on site-specific AP substrates, borohydride trapping, Mg2+-dependence

    PMID:9358166

    Open questions at the time
    • Tested in yeast Ogg1; relative contribution in human cells with APE1 present not quantified
  3. 1999 High

    Demonstrated OGG1 is the major physiological 8-oxoG glycosylase in vivo, since its loss eliminates extract nicking activity and causes age-dependent 8-oxoG accumulation in tissue DNA.

    Evidence Immunodepletion of endogenous type-1a protein and Mmh knockout mouse with LC/MS quantification of tissue 8-oxoG

    PMID:10329432 PMID:11978483

    Open questions at the time
    • Residual repair activity in knockout indicates backup pathways not defined
    • Tissue-specific consequences not fully mapped
  4. 2000 Medium

    Resolved how a single gene serves both genomes by showing alternative splicing produces a nuclear α-isoform and a mitochondria-targeted β-isoform.

    Evidence Subcellular fractionation and isoform-specific Western blotting of nuclear and mitochondrial fractions

    PMID:10775435 PMID:11554314

    Open questions at the time
    • Relative repair contribution of each isoform not quantified
    • Later revised by evidence that α-OGG1 also enters mitochondria
  5. 2002 High

    Established the functional importance of mitochondrial OGG1 by showing that targeting it to mitochondria accelerates mtDNA repair and improves survival under oxidative stress.

    Evidence Tetracycline-regulated MnSOD-MLS-OGG1 expression with mtDNA repair and cell-survival assays

    PMID:12244119

    Open questions at the time
    • Used an engineered targeting sequence rather than endogenous import
    • Mechanism of endogenous mitochondrial import unaddressed
  6. 2002 Medium

    Connected OGG1 to the wider repair machinery by placing it in a CSB-containing complex, while showing the interaction is indirect.

    Evidence His-tag pull-down and co-localization after γ-irradiation, with negative direct-interaction results by EMSA, Y2H, and incision assay

    PMID:12531019

    Open questions at the time
    • Bridging factors in the larger complex not identified
    • Functional consequence of the complex for repair kinetics unclear
  7. 2005 Medium

    Linked OGG1 localization dynamics to the cell cycle and revealed a functional consequence of the common Ser326Cys polymorphism in nucleolar relocalization.

    Evidence Live-cell EGFP-hOGG1 imaging with cell-cycle synchronization, transcription inhibition, and phosphorylation analysis

    PMID:15800211

    Open questions at the time
    • Functional purpose of S-phase nucleolar relocalization unresolved
    • Kinase responsible for the phosphorylation not identified
  8. 2007 Medium

    Identified an upstream transcriptional control of OGG1 abundance via TSC2/NF-YA, explaining how cellular signaling sets repair capacity.

    Evidence TSC2 knockdown/knockout, NF-YA EMSA and ChIP at the OGG1 promoter, CAAT-box reporter mutagenesis, and TSC2 rescue

    PMID:17989114

    Open questions at the time
    • Generality across cell types not established
    • Link between TSC2 signaling and oxidative-stress responsiveness of OGG1 unclear
  9. 2014 High

    Defined the biophysical lesion-search mechanism, showing OGG1 finds 8-oxoG through combined sliding and hopping rather than pure 1D sliding.

    Evidence Single-molecule molecular-clock assay with covalent phosphate roadblocks and numerical simulation

    PMID:25016526

    Open questions at the time
    • Search behavior on chromatinized DNA in vivo not addressed
  10. 2015 High

    Provided pharmacological tools and mechanism-of-action by identifying selective inhibitors that block Schiff-base formation without preventing substrate binding.

    Evidence High-throughput screen with three orthogonal biochemical assays, Schiff-base trapping, EMSA, and selectivity panel

    PMID:26218629

    Open questions at the time
    • Cellular and in vivo efficacy not tested in this study
  11. 2016 Medium

    Extended OGG1 function beyond repair to epigenetic regulation, showing it recruits TET1 to drive oxidative-stress-induced DNA demethylation.

    Evidence Co-IP of OGG1 and TET1 with siRNA knockdown/overexpression and methylation analysis after oxidative stress

    PMID:27251462

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation of the OGG1–TET1 interface
    • Genome-wide scope of affected loci not mapped
  12. 2017 Medium

    Defined a non-catalytic gene-regulatory role, showing OGG1 binding to 8-oxoG enhances NF-κB DNA occupancy and target-gene expression independent of excision.

    Evidence EMSA with purified NF-κB on 8-oxoG-containing Cxcl2 promoter oligos plus siRNA, reporter, and qRT-PCR

    PMID:28266569

    Open questions at the time
    • Structural basis for facilitated NF-κB recruitment not resolved
    • In vivo relevance to inflammation not tested here
  13. 2018 Medium

    Revealed OGG1-initiated repair can be cytotoxic, showing it generates strand breaks that hyperactivate PARP1 to drive caspase-independent parthanatos.

    Evidence OGG1 KO/siRNA and repair-deficient mutants with strand-break, PARP1 activation, AIF translocation, and cell-death readouts

    PMID:29795387

    Open questions at the time
    • Threshold of oxidative stress that switches repair to death not defined
    • Tissue contexts where this dominates unclear
  14. 2018 High

    Revised the localization model by showing the canonical nuclear α-OGG1 isoform also imports into mitochondrial nucleoids and is required to protect the mitochondrial network.

    Evidence Subcellular fractionation, super-resolution imaging of nucleoids, and catalytically dead mutant under oxidative stress

    PMID:29848661

    Open questions at the time
    • Quantitative split of α-OGG1 between compartments not established
    • Import machinery used by α-OGG1 not identified
  15. 2020 Medium

    Sharpened the non-catalytic model by showing substrate binding, not excision, drives inflammatory gene activation, with excision-deficient OGG1 more potent than wild-type.

    Evidence Structure-function with K249Q and substrate-binding-impaired mutants, ChIP, and qRT-PCR in OGG1-null cells

    PMID:32378256

    Open questions at the time
    • How binding-competent stalled OGG1 reshapes local chromatin not resolved
  16. 2020 High

    Identified RECQL4 as a direct stimulatory partner of OGG1 and placed it under SIRT1/deacetylation control, defining a regulatory axis for repair efficiency.

    Evidence Reciprocal Co-IP, in vitro OGG1 activity assay with recombinant RECQL4, SIRT1 deacetylation reconstitution, and 8-oxoG quantification

    PMID:32432680

    Open questions at the time
    • Acetylation sites on RECQL4 governing the interaction not pinpointed
    • Direct structural contact surface unmapped
  17. 2020 Medium

    Established a chromatin-recruitment requirement for OGG1, identifying cohesin and Mediator (CDK8, MED12) as factors needed for stress-induced chromatin relocalization and repair.

    Evidence siRNA screen validated by OGG1–Mediator Co-IP, chromatin-binding assays, and 8-oxoG quantification

    PMID:32710616

    Open questions at the time
    • Whether the interaction is direct or scaffold-mediated unclear
    • Mechanism coupling Mediator to lesion targeting unresolved
  18. 2020 High

    Mapped the catalytic chemistry to specific cysteines, separating residues essential for glycosylase versus lyase activity and structural stability.

    Evidence Systematic site-directed cysteine mutagenesis with in vitro glycosylase and lyase assays on each mutant

    PMID:33203705

    Open questions at the time
    • In vivo functional consequences of individual cysteine loss not tested
  19. 2020 Medium

    Validated a substrate-binding inhibitor (TH5487) in cells, showing blockade of chromatin binding reduces 8-oxoG incision and downstream double-strand breaks.

    Evidence Live-cell GFP-OGG1 recruitment imaging, chromatin fractionation, laser microirradiation, and strand-break measurement

    PMID:33114607

    Open questions at the time
    • Specificity and off-target profile in vivo not fully characterized
  20. 2020 Medium

    Identified a small-molecule cofactor, ubiquinol, that directly stimulates OGG1 and shifts its bifunctional balance toward glycosylase activity.

    Evidence Real-time BER assay with purified OGG1, melting-curve analysis, and exclusion of redox/expression effects

    PMID:31923624

    Open questions at the time
    • Single-method support for the direct interaction; binding site not defined
    • Physiological relevance of ubiquinol modulation in cells unestablished
  21. 2021 High

    Linked OGG1-deficiency to chemotherapy response, showing unrepaired 8-oxoG creates replication blocks that sensitize AML cells to cytarabine.

    Evidence In vitro replication assay with purified Pol δ on 8-oxo-dG templates plus OGG1-deficient AML cell cytotoxicity and fragile-site analysis

    PMID:33836581

    Open questions at the time
    • Therapeutic window and in vivo validation not addressed
    • Generality across other replication-targeting drugs unclear
  22. 2022 High

    Demonstrated chemical reprogramming of OGG1 catalysis, with TH10785 binding F319/G42 to add a β,δ-lyase activity that reroutes repair to an APE1-independent, PNKP1-dependent pathway.

    Evidence OGG1–TH10785 crystal structure, F319/G42 mutagenesis, in vitro enzymatic and pathway-dependency assays, and cellular recruitment imaging

    PMID:35737787

    Open questions at the time
    • Whether such activator-driven rerouting confers therapeutic benefit in disease models unaddressed
  23. 2022 Medium

    Defined post-translational control of OGG1 abundance, identifying NEDD4L as the E3 ligase that ubiquitinates OGG1 for degradation under TGF-β1 signaling.

    Evidence NEDD4L knockdown, ubiquitination and stability assays, proteasome rescue, and TH5487 treatment in cells and fibrotic lung model

    PMID:35654123

    Open questions at the time
    • Ubiquitination sites on OGG1 not mapped
    • Whether NEDD4L acts on both isoforms unclear
  24. 2023 Medium

    Established OGG1 as a pioneer-like factor in fibrosis, showing it recruits phospho-SMAD3 to pro-fibrotic promoters and that substrate-binding inhibition blocks lung remodeling.

    Evidence OGG1 and SMAD3 ChIP-seq, ATAC-seq, TH5487 inhibition, and OGG1 KO mice in a TGF-β1 fibrosis model

    PMID:36651270

    Open questions at the time
    • Direct OGG1–SMAD3 contact versus chromatin-mediated cooperation not distinguished
  25. 2023 Medium

    Connected mitochondrial OGG1 to innate-immune signaling, showing it limits cytoplasmic mtDNA release and STING activation to reduce age-associated neuroinflammation.

    Evidence mtOGG1-transgenic mice and LPS-challenged HMC3 cells with cytokine, cytoplasmic mtDNA, and pSTING readouts

    PMID:37011700

    Open questions at the time
    • Sex-specific (male-only) response mechanism unexplained
    • Whether endogenous mtOGG1 levels suffice for this protection unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and mechanistic basis by which substrate-bound, catalytically stalled OGG1 acts as a pioneer factor to recruit specific transcription factors (NF-κB, SMAD3) and remodel chromatin remains unresolved.
  • No structure of OGG1–transcription factor–chromatin assembly
  • Whether recruitment is direct or chromatin-mediated undetermined
  • Rules selecting which genes are regulated versus repaired are unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 4 GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CDK8CSBNEDD4LNFKBRECQL4SIRT1SMAD3TET1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Human OGG1 (hOGG1/hMMH) encodes a DNA glycosylase/AP lyase that excises 8-oxoguanine (8-oxoG) from duplex DNA, with strong preference for 8-oxoG:C base pairs over 8-oxoG:A; the cloned human cDNA complements an E. coli fpg mutant and restores wild-type mutation rate in an OGG1-deficient yeast strain. Expression of hOGG1 in fpg-deficient E. coli (lyase activity assay on site-specific 8-oxoG substrates); complementation of yeast ogg1 mutator phenotype; substrate-specificity assays Proceedings of the National Academy of Sciences of the United States of America High 9187114 9223305
1997 The yeast Ogg1 protein possesses, in addition to N-glycosylase/AP lyase activity, a deoxyribophosphodiesterase (dRpase) activity that removes the sugar-phosphate residue at incised 5' AP sites and processes 3'-incised AP sites in an Mg2+-dependent manner, leaving a one-nucleotide gap directly fillable by DNA polymerase without additional enzymes. In vitro dRpase assay using purified GST-Ogg1 fusion protein with site-specific AP-site substrates; borohydride trapping; MgCl2-dependent activity assays Nucleic acids research High 9358166
1999 Endogenous hMMH (hOGG1) type 1a protein is the major 8-OH-G glycosylase/AP lyase in human cells; immunodepletion of type 1a from whole-cell extracts eliminates most AP lyase activity, and targeted disruption of the mouse Mmh gene abolishes liver-extract nicking activity at 8-OH-G, leading to progressive accumulation of 8-oxoG in liver DNA with age. Immunodepletion with type-1a-specific antibody; knockout mouse generation; enzyme activity assay on 8-oxoG-containing substrates; LC/MS quantification of 8-oxoG in tissue DNA Biochemical and biophysical research communications High 10329432 11978483
2000 Alpha-hOgg1 protein (the predominant nuclear isoform) localizes to the nucleus and is directed there by a nuclear localization signal; beta-hOgg1 carries a mitochondrial targeting signal and is directed to mitochondria; these localizations arise from alternative splicing of a single mRNA. Subcellular fractionation; Western blot with isoform-specific antibodies; detection of authentic hOGG1 protein in mitochondrial and nuclear fractions from human cells Archives of biochemistry and biophysics Medium 10775435 11554314
2002 Conditional targeting of recombinant OGG1 (bearing the MnSOD mitochondrial localization sequence) to mitochondria in transfected cells increases repair of oxidative damage in mtDNA ~8-fold and improves cell survival following oxidative stress. Tetracycline-regulated expression vector with MnSOD MLS fused to OGG1; Western blot of mitochondrial extracts; enzyme activity assay; cell survival after oxidative stress; DNA repair assay The Journal of biological chemistry High 12244119
2002 CSB (Cockayne syndrome group B protein) contributes to hOgg1-mediated 8-OH-G base excision repair; pull-down of hOgg1 by histidine-tagged CSB and co-localization after γ-irradiation indicate they co-exist in a complex in vivo, but purified CSB and purified hOgg1 do not interact directly (no direct protein-protein interaction detected by incision assay, gel shift, or yeast two-hybrid), suggesting they interact within a larger complex. His-tag pull-down; co-localization by immunofluorescence after γ-irradiation; anti-CSB antibody depletion of cell extracts; EMSA; yeast two-hybrid; incision activity assay DNA repair Medium 12531019
2005 hOGG1 dynamically relocalizes to the nucleolus during S-phase in a transcription-dependent manner. The Ser326Cys polymorphic variant (hOGG1-Cys326) fails to relocalize to nucleoli during S-phase due to an altered phosphorylation status. Live-cell imaging of EGFP-hOGG1 fusion in stably transfected cell line; cell-cycle synchronization; transcription inhibition; phosphorylation-state analysis Nucleic acids research Medium 15800211
2014 hOGG1 searches DNA by microscopic 2D and 3D steps that macroscopically appear as 1D sliding; strand-transfer events (hopping) dominate over true sliding at distances longer than ~7 phosphate linkages, as shown by covalent phosphate roadblocks between closely spaced damage sites having little effect on inter-site transfers. High-resolution molecular clock single-molecule assay; covalent phosphate-roadblock experiments; numerical simulations constrained by experimental transfer rates Nucleic acids research High 25016526
2015 Small-molecule OGG1 inhibitors (hydrazides/acyl hydrazones; IC50 <1 μM) block catalysis by inhibiting Schiff base formation during the glycosylase reaction without preventing OGG1 binding to 8-oxoG-containing DNA substrate; these compounds show >100-fold selectivity for OGG1 over other DNA glycosylases. Fluorescence-based high-throughput screen (~50,000 compounds); IC50 determination by three independent biochemical assays; Schiff-base trapping assay; DNA-binding EMSA; selectivity panel against other glycosylases ACS chemical biology High 26218629
2016 OGG1 promotes oxidative stress-induced DNA demethylation by binding to 8-oxoG lesions and recruiting the TET1 dioxygenase to the lesion site; OGG1 knockdown prevents oxidative stress-induced demethylation, while OGG1 overexpression enhances it. Co-immunoprecipitation of OGG1 and TET1; siRNA knockdown and overexpression; methylation analysis after oxidative stress Cellular signalling Medium 27251462
2017 OGG1 (but not catalytic activity per se) facilitates NF-κB binding to DNA at promoters containing 8-oxoG; OGG1 interaction with 8-oxoG positioned outside the NF-κB consensus motif enhances purified NF-κB DNA occupancy; OGG1 is required for NF-κB-dependent gene expression prior to 8-oxoG excision. EMSA with synthetic 8-oxoG-containing oligonucleotides from Cxcl2 promoter; purified NF-κB binding assay; OGG1 siRNA depletion; luciferase reporter assay; qRT-PCR of NF-κB target genes Scientific reports Medium 28266569
2018 OGG1-initiated BER generates DNA strand breaks and AP sites under excessive oxidative stress that hyperactivate PARP1, leading to AIF nuclear translocation and caspase-independent cell death (parthanatos); cells expressing repair-deficient OGG1 mutants or lacking OGG1 show lower strand breaks, reduced PARP1 activation, and increased resistance to ROS-induced parthanatos. OGG1 knockout/siRNA MEFs and neuroblastoma cells; expression of repair-deficient OGG1 mutants; measurement of DNA strand breaks, PARP1 activation, AIF nuclear translocation; cell death assays Cell death & disease Medium 29795387
2018 The α-OGG1 isoform (previously considered exclusively nuclear) contains a functional mitochondrial-targeting sequence, is imported into mitochondria, and associates with mtDNA in nucleoids; enzymatic activity of mitochondrial α-OGG1 is required to preserve the mitochondrial network under oxidative stress. Subcellular fractionation; super-resolution microscopy of mitochondrial nucleoids; expression of catalytically dead α-OGG1 mutant; mitochondrial network morphology assessment after oxidative stress Journal of cell science High 29848661
2020 OGG1 binding to 8-oxoG at gene regulatory regions (not its catalytic excision activity) is the primary mechanism for modulating inflammatory gene expression; excision-deficient K249Q OGG1 mutant activates pro-inflammatory gene expression more potently than wild-type, whereas a substrate-binding-impaired OGG1 mutant has no effect. Transfection of wild-type vs. repair-deficient (K249Q) and substrate-binding-impaired OGG1 mutants into OGG1 knockout/depleted cells; chromatin immunoprecipitation (ChIP); gene expression (qRT-PCR); cysteine oxidation state analysis FASEB journal Medium 32378256
2020 RECQL4 DNA helicase physically interacts with OGG1 and stimulates its catalytic activity; RECQL4 deficiency impairs 8-oxoG repair and increases genomic 8-oxoG levels; SIRT1 deacetylates RECQL4 in vitro and in cells, controlling the OGG1–RECQL4 interaction by maintaining RECQL4 in a hypoacetylated state after oxidative stress. Co-immunoprecipitation; in vitro deacetylation assay with recombinant SIRT1; OGG1 activity assay with and without recombinant RECQL4; 8-oxoG quantification in RECQL4-deficient cells; ChIP Nucleic acids research High 32432680
2020 Cohesin and Mediator complex subunits (including CDK8 and MED12) are required for OGG1 relocalization to chromatin upon oxidative stress and for efficient 8-oxoG removal; CDK8 and MED12 physically interact with OGG1 in response to oxidative stress. High-throughput siRNA screen; Co-IP of OGG1 with Mediator subunits; 8-oxoG quantification after knockdown; chromatin-binding assay for OGG1 after oxidative stress Nucleic acids research Medium 32710616
2020 Cysteine residues of OGG1 fall into four functional categories: C146 and C255 are necessary for glycosylase activity; C140, C163, C241, and C253 are required for lyase activity; C253 contributes to structural stability; C28 and C75 have no known catalytic function. Site-directed mutagenesis of each cysteine residue followed by biochemical characterization of glycosylase and lyase activities of purified mutant proteins The Journal of biological chemistry High 33203705
2022 Small molecule TH10785 binds OGG1 at phenylalanine-319 and glycine-42, increases glycosylase activity ~10-fold, and generates a novel β,δ-lyase enzymatic function; this alters the BER pathway so that repair no longer requires APE1 but becomes dependent on PNKP1 activity. Crystal structure of OGG1–TH10785 complex; site-directed mutagenesis of F319 and G42; in vitro enzymatic assays; PNKP1 dependence assay; cellular OGG1 recruitment imaging; APE1 independence demonstrated biochemically and in cells Science (New York, N.Y.) High 35737787
2007 Tuberin (TSC2) regulates OGG1 expression at the transcriptional level via the transcription factor NF-YA binding to CAAT boxes in the OGG1 promoter; TSC2-deficient cells have markedly decreased OGG1 mRNA, protein, and activity, with accumulation of 8-oxodG, and re-introduction of TSC2 cDNA restores NF-YA and OGG1 expression. TSC2 siRNA knockdown in human cells; TSC2-/- and TSC2+/- MEFs; gel-shift (EMSA) for NF-YA binding; ChIP of NF-YA at OGG1 promoter; luciferase reporter with mutated CAAT boxes; OGG1 activity assay American journal of physiology. Renal physiology Medium 17989114
2022 NEDD4L E3 ubiquitin ligase ubiquitinates OGG1 and targets it for proteasomal degradation; TGF-β1 suppresses NEDD4L expression, thereby stabilizing OGG1 protein and promoting EMT/fibrosis; the OGG1 inhibitor TH5487 cancels TGF-β1-mediated NEDD4L suppression, restoring NEDD4L-mediated OGG1 degradation. NEDD4L siRNA knockdown; OGG1 protein stability assay; ubiquitination assay; proteasome inhibitor rescue; adeno-associated virus OGG1 overexpression in fibrotic lungs; TH5487 treatment in cells and mouse model Chemico-biological interactions Medium 35654123
2023 OGG1 complexed with 8-oxoG in open chromatin acts as a pioneer factor that recruits phosphorylated SMAD3 to pro-fibrotic gene promoters; pharmacological inhibition of OGG1 substrate binding (TH5487) abrogates fibrotic gene expression and lung remodeling in a TGF-β1 mouse model. ChIP-seq for OGG1 and SMAD3; ATAC-seq; TH5487 pharmacological inhibition; OGG1 KO mice; qRT-PCR; lung fibrosis model (TGF-β1 instillation) Nucleic acids research Medium 36651270
2021 In vitro replication assays demonstrate that DNA polymerase δ inserts cytarabine (Ara-C) opposite unrepaired 8-oxo-dG, causing termination of DNA synthesis; OGG1-deficient AML cells show enhanced sensitivity to Ara-C due to endogenous 8-oxo-dG accumulation generating replication blocks at common fragile sites. In vitro DNA replication assay with purified DNA polymerase δ and 8-oxo-dG templates; OGG1-deficient AML cell lines; Ara-C cytotoxicity assay; DNA strand-break measurement; common fragile site analysis Proceedings of the National Academy of Sciences of the United States of America High 33836581
2020 The OGG1 inhibitor TH5487 binds the OGG1 active site, impairs chromatin binding of OGG1, reduces OGG1 recruitment to oxidative DNA damage sites, prevents 8-oxoG incision, and results in fewer DNA double-strand breaks in oxidatively stressed cells. Live-cell imaging of GFP-OGG1 recruitment kinetics; 8-oxoG immunofluorescence; DNA strand-break measurement; chromatin fractionation; laser-induced DNA damage Biomolecules Medium 33114607
2020 The direct activity of purified hOGG1 is increased in a concentration-dependent manner by ubiquinol through a direct interaction (not via changes in redox state or gene expression); ubiquinol shifts OGG1 bifunctionality toward increased N-glycosylase activity and facilitates dissolution of the enzyme's end-product complex with the unsaturated 3'-phospho-α,β-aldehyde DNA terminus. Real-time base excision repair assay with purified OGG1 and commercially obtained OGG1; mitochondria-isolated OGG1; melting curve analysis; gene expression analysis; cellular redox state measurement DNA repair Medium 31923624
2023 Elevated mitochondrially-targeted OGG1 (mtOGG1) reduces age-associated neuroinflammation by decreasing cytoplasmic mtDNA release after LPS induction and suppressing the STING pathway; mtOGG1Tg mice show decreased TNFα, pro-inflammatory cytokines, and resistance to STING activation (sex-specific: male mice only responded). Transgenic mtOGG1-overexpressing mice; cytokine multiplex assay; cytoplasmic mtDNA quantification; pSTING pathway Western blot; LPS-challenged HMC3 cells overexpressing mtOGG1; mitochondrial function assay Free radical biology & medicine Medium 37011700

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 566 1495996
1997 Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 546 9223305
2000 The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Archives of biochemistry and biophysics 405 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
2002 Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an alternative pathway for the repair of 8-oxoguanine and other oxidation products in DNA. Nucleic acids research 244 12433996
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 206 15584022
2016 Ogg1-Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis. Circulation research 162 27384322
2003 DNA lesion recognition by the bacterial repair enzyme MutM. The Journal of biological chemistry 154 14525999
2002 Structural insights into lesion recognition and repair by the bacterial 8-oxoguanine DNA glycosylase MutM. Nature structural biology 153 12055620
2001 Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. International journal of cancer 141 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 133 11554314
2001 The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis. Antioxidants & redox signaling 130 11554447
2000 Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from an extreme thermophile, Thermus thermophilus HB8. The EMBO journal 128 10921868
2003 Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 127 14578150
2006 Oxidative damage to purines in DNA: role of mammalian Ogg1. DNA repair 113 17127104
2012 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PloS one 110 23284747
2000 Characterization of the hOGG1 promoter and its expression during the cell cycle. Mutation research 105 11018584
2003 Interactions among the Escherichia coli mutT, mutM, and mutY damage prevention pathways. DNA repair 99 12531387
2004 The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk. Pharmacogenetics 90 15077011
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 83 26218629
2016 OGG1 is essential in oxidative stress induced DNA demethylation. Cellular signalling 82 27251462
2018 OGG1-initiated base excision repair exacerbates oxidative stress-induced parthanatos. Cell death & disease 79 29795387
2005 Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant. Nucleic acids research 79 15800211
2002 Involvement of mammalian OGG1(MMH) in excision of the 8-hydroxyguanine residue in DNA. Free radical biology & medicine 76 11978483
2008 The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 75 18628426
2017 OGG1-DNA interactions facilitate NF-κB binding to DNA targets. Scientific reports 72 28266569
2018 The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. Scientific reports 68 30291284
2005 Oxidized guanine lesions and hOgg1 activity in lung cancer. Oncogene 64 15856018
2022 Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function. Science (New York, N.Y.) 61 35737787
2018 Searching for assay controls for the Fpg- and hOGG1-modified comet assay. Mutagenesis 54 28992346
2007 OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study. Mutation research 54 18155253
2010 The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis. Breast cancer research and treatment 53 20058067
2020 Targeting OGG1 arrests cancer cell proliferation by inducing replication stress. Nucleic acids research 51 33211885
2018 Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer. Pharmacology & therapeutics 51 30240635
1999 Human MMH (OGG1) type 1a protein is a major enzyme for repair of 8-hydroxyguanine lesions in human cells. Biochemical and biophysical research communications 50 10329432
2014 PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1. PloS one 49 25526641
2019 Roles of OGG1 in transcriptional regulation and maintenance of metabolic homeostasis. DNA repair 48 31311771
2009 Polymorphisms in hOGG1 and XRCC1 and risk of prostate cancer: effects modified by plasma antioxidants. Urology 47 19914697
2015 Mitochondrial DNA Repair through OGG1 Activity Attenuates Breast Cancer Progression and Metastasis. Cancer research 43 26586787
2020 Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 42 32378256
2011 Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity. Free radical biology & medicine 42 22019439
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
1997 Augmented expression of a human gene for 8-oxoguanine DNA glycosylase (MutM) in B lymphocytes of the dark zone in lymph node germinal centers. The Journal of experimental medicine 41 9348312
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
2014 Microscopic mechanism of DNA damage searching by hOGG1. Nucleic acids research 37 25016526
2011 XRCC1 and hOGG1 genes and risk of nasopharyngeal carcinoma in North African countries. Molecular carcinogenesis 35 21520294
2020 The role of cysteines in the structure and function of OGG1. The Journal of biological chemistry 34 33203705
1997 The yeast 8-oxoguanine DNA glycosylase (Ogg1) contains a DNA deoxyribophosphodiesterase (dRpase) activity. Nucleic acids research 34 9358166
2017 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. PloS one 33 28727777
1998 Sequence analysis of mutA and mutM genes involved in the biosynthesis of the lantibiotic mutacin II in Streptococcus mutans. Gene 33 9461412
2000 Detection of 8-oxoG DNA glycosylase activity and OGG1 transcripts in the rat CNS. Mutation research 32 10882853
1995 Spectra of superoxide-induced mutations in the lacI gene of a wild-type and a mutM strain of Escherichia coli K-12. Mutation research 32 7529882
2020 Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome? International journal of molecular sciences 31 33171795
2007 Tuberin regulates the DNA repair enzyme OGG1. American journal of physiology. Renal physiology 31 17989114
2025 Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis. Journal of biomedical science 28 39741341
2023 8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury. Nucleic acids research 28 36651270
2023 OGG1 aggravates renal ischemia-reperfusion injury by repressing PINK1-mediated mitophagy. Cell proliferation 28 36788635
2023 Mitochondrial OGG1 expression reduces age-associated neuroinflammation by regulating cytosolic mitochondrial DNA. Free radical biology & medicine 28 37011700
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
2012 The Presence of the DNA Repair Genes mutM, mutY, mutL, and mutS is Related to Proteome Size in Bacterial Genomes. Frontiers in genetics 28 22403581
2018 Overexpression of MTH1 and OGG1 proteins in ulcerative colitis-associated carcinogenesis. Oncology letters 27 30008864
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
2022 OGG1 in the Kidney: Beyond Base Excision Repair. Oxidative medicine and cellular longevity 26 36620083
2018 Decreased 8-oxoguanine DNA glycosylase 1 (hOGG1) expression and DNA oxidation damage induced by Cr (VI). Chemico-biological interactions 26 30496737
2015 OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data. Disease markers 26 26089588
2013 Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer's disease mouse model. Mechanisms of ageing and development 26 24121118
2001 Mammalian Ogg1/Mmh gene plays a major role in repair of the 8-hydroxyguanine lesion in DNA. Progress in nucleic acid research and molecular biology 26 11554290
2020 OGG1 Inhibitor TH5487 Alters OGG1 Chromatin Dynamics and Prevents Incisions. Biomolecules 24 33114607
2012 The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells. Biochemical and biophysical research communications 24 22564741
2020 Chromatin recruitment of OGG1 requires cohesin and mediator and is essential for efficient 8-oxoG removal. Nucleic acids research 23 32710616
2019 Dual Inhibitors of 8-Oxoguanine Surveillance by OGG1 and NUDT1. ACS chemical biology 23 31622553
2016 Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce CAG/CTG repeat instability. Nucleic acids research 23 26980281
2022 Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions. Journal of innate immunity 22 35512649
2022 Pharmacological OGG1 inhibition decreases murine allergic airway inflammation. Frontiers in pharmacology 22 36324676
2021 NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487. International journal of molecular sciences 22 33925271
2014 Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis. Diagnostic pathology 22 24893568
2018 Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1. Journal of cell science 21 29848661
2016 The hOGG1 Ser326Cys Gene Polymorphism and Breast Cancer Risk in Saudi Population. Pathology oncology research : POR 21 27822728
2015 Role of Bacillus subtilis DNA Glycosylase MutM in Counteracting Oxidatively Induced DNA Damage and in Stationary-Phase-Associated Mutagenesis. Journal of bacteriology 21 25825434
2013 Structural and biochemical analysis of DNA helix invasion by the bacterial 8-oxoguanine DNA glycosylase MutM. The Journal of biological chemistry 21 23404556
1999 Structure and chromosome location of human OGG1. Cytogenetics and cell genetics 21 10449904
2009 DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients. Journal of biomedicine & biotechnology 20 19885394
2007 Genetic analysis of CC16, OGG1 and GCLC polymorphisms and susceptibility to COPD. Respirology (Carlton, Vic.) 20 17207022
2022 TH5487, a small molecule inhibitor of OGG1, attenuates pulmonary fibrosis by NEDD4L-mediated OGG1 degradation. Chemico-biological interactions 19 35654123
2011 Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM). FEMS microbiology letters 18 22092761
2021 Enhanced cytarabine-induced killing in OGG1-deficient acute myeloid leukemia cells. Proceedings of the National Academy of Sciences of the United States of America 17 33836581
2016 XPC deficiency is related to APE1 and OGG1 expression and function. Mutation research 17 26811994
2013 Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth. Molecules and cells 17 23677377
2022 Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases. Basic & clinical pharmacology & toxicology 16 35708697
2012 Sequence-dependent structural variation in DNA undergoing intrahelical inspection by the DNA glycosylase MutM. The Journal of biological chemistry 16 22465958
2009 Analysis of an anomalous mutant of MutM DNA glycosylase leads to new insights into the catalytic mechanism. Journal of the American Chemical Society 16 19961158
1990 Purification and properties of a recombinant DNA-derived ovine growth hormone analogue (oGH1) expressed in Escherichia coli. Journal of molecular endocrinology 16 2182044
2020 The activity of the DNA repair enzyme hOGG1 can be directly modulated by ubiquinol. DNA repair 15 31923624
2017 8-oxoguanine DNA glycosylase (Ogg1) controls hepatic gluconeogenesis. DNA repair 15 29207315

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