DNA Sequence Context Effects on the Glycosylase Activity of Human 8-Oxoguanine DNA Glycosylase*

Background: Human 8-oxoguanine DNA glycosylase (OGG1) removes the mutagenic DNA lesion 7,8-dihydro-8-oxoguanine. Results: OGG1 activity is significantly decreased by an adjacent DNA mismatch. Conclusion: Tandem lesions can dramatically diminish base excision repair. Significance: Deamination of 5′-methylcytosine in CpG-rich DNA sequences prone to oxidative DNA damage could be a significant factor in the generation of G to T transversions hot spots. Human 8-oxoguanine DNA glycosylase (OGG1) is a key enzyme involved in removing 7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic DNA lesion generated by oxidative stress. The removal of 8-oxoG by OGG1 is affected by the local DNA sequence, and this feature most likely contributes to observed mutational hot spots in genomic DNA. To elucidate the influence of local DNA sequence on 8-oxoG excision activity of OGG1, we conducted steady-state, pre-steady-state, and single turnover kinetic evaluation of OGG1 in alternate DNA sequence contexts. The sequence context effect was studied for a mutational hot spot at a CpG dinucleotide. Altering either the global DNA sequence or the 5′-flanking unmodified base pair failed to influence the excision of 8-oxoG. Methylation of the cytosine 5′ to 8-oxoG also did not affect 8-oxoG excision. In contrast, a 5′-neighboring mismatch strongly decreased the rate of 8-oxoG base removal. Substituting the 5′-C in the CpG dinucleotide with T, A, or tetrahydrofuran (i.e. T:G, A:G, and tetrahydrofuran:G mispairs) resulted in a 10-, 13-, and 4-fold decrease in the rate constant for 8-oxoG excision, respectively. A greater loss in activity was observed when T:C or A:C was positioned 5′ of 8-oxoG (59- and 108-fold, respectively). These results indicate that neighboring structural abnormalities 5′ to 8-oxoG deter its repair thereby enhancing its mutagenic potential.

• Publication year

  2012

• Venue

  Journal of Biological Chemistry

• Publication date

  2012-09-19

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M112.397786PMID 22989888PMCID PMC3481274
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Surprising repair activities of nonpolar analogs of 8-oxoG expose features of recognition and catalysis by base excision repair glycosylases.

  2012cited by this paper
• Sequence-dependent Structural Variation in DNA Undergoing Intrahelical Inspection by the DNA glycosylase MutM*

  2012influential reference
• Poly(ADP-ribose) Polymerase 1 (PARP-1) Binds to 8-Oxoguanine-DNA Glycosylase (OGG1)*

  2011cited by this paper
• Thermodynamic and kinetic basis for recognition and repair of 8-oxoguanine in DNA by human 8-oxoguanine-DNA glycosylase

  2011cited by this paper
• Separation-of-function mutants unravel the dual-reaction mode of human 8-oxoguanine DNA glycosylase.

  2011cited by this paper
• Efficient formation of the tandem thymine glycol/8-oxo-7,8-dihydroguanine lesion in isolated DNA and the mutagenic and cytotoxic properties of the tandem lesions in Escherichia coli cells.

  2010influential reference
• Mutual relationship between stacking and hydrogen bonding in DNA. Theoretical study of guanine-cytosine, guanine-5-methylcytosine, and their dimers.

  2010cited by this paper
• In vitro replication and repair studies of tandem lesions containing neighboring thymidine glycol and 8-oxo-7,8-dihydro-2'-deoxyguanosine.

  2009influential reference
• Epigenetics, oxidative stress, and Alzheimer disease.

  2009influential reference
• The cis-(5R,6S)-Thymine Glycol Lesion Occupies the Wobble Position When Mismatched with Deoxyguanosine in DNA†

  2009cited by this paper
• Interconversion of the cis-5R,6S- and trans-5R,6R-Thymine Glycol Lesions in Duplex DNA

  2008cited by this paper
• Quantification of oxidative single-base and intrastrand cross-link lesions in unmethylated and CpG-methylated DNA induced by Fenton-type reagents

  2007cited by this paper
• OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells

  2007cited by this paper
• Structural Characterization of Human 8-Oxoguanine DNA Glycosylase Variants Bearing Active Site Mutations*

  2007cited by this paper
• A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex

  2006cited by this paper
• Human DNA ligases I, III, and IV-purification and new specific assays for these enzymes.

  2006cited by this paper
• Product inhibition and magnesium modulate the dual reaction mode of hOgg1.

  2005cited by this paper
• Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA

  2005cited by this paper
• Kinetics of substrate recognition and cleavage by human 8-oxoguanine-DNA glycosylase

  2005cited by this paper
• Mutagenesis of 8-oxoguanine adjacent to an abasic site in simian kidney cells: tandem mutations and enhancement of G-->T transversions.

  2005cited by this paper
• Structure and Energetics of Clustered Damage Sites

  2005cited by this paper
• The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis.

  2004cited by this paper
• AP endonuclease and poly(ADP-ribose) polymerase-1 interact with the same base excision repair intermediate.

  2004cited by this paper
• Deficiencies in mouse Myh and Ogg1 result in tumor predisposition and G to T mutations in codon 12 of the K-ras oncogene in lung tumors.

  2004cited by this paper
• Influence of DNA structure on DNA polymerase beta active site function: extension of mutagenic DNA intermediates.

  2004cited by this paper
• Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2).

  2004cited by this paper
• DNA Lesion Recognition by the Bacterial Repair Enzyme MutM*

  2003influential reference
• Suppressive activities of OGG1 and MYH proteins against G:C to T:A mutations caused by 8-hydroxyguanine but not by benzo[a]pyrene diol epoxide in human cells in vivo.

  2003cited by this paper
• Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption.

  2003cited by this paper
• Strand-specific processing of 8-oxoguanine by the human mismatch repair pathway: inefficient removal of 8-oxoguanine paired with adenine or cytosine.

  2003cited by this paper
• Role of XRCC1 in the Coordination and Stimulation of Oxidative DNA Damage Repair Initiated by the DNA Glycosylase hOGG1*

  2003cited by this paper
• The mammalian mismatch repair pathway removes DNA 8-oxodGMP incorporated from the oxidized dNTP pool.

  2002cited by this paper
• Oxidative DNA damage induced by copper and hydrogen peroxide promotes CG-->TT tandem mutations at methylated CpG dinucleotides in nucleotide excision repair-deficient cells.

  2002cited by this paper
• OGG1 protein suppresses G:C-->T:A mutation in a shuttle vector containing 8-hydroxyguanine in human cells.

  2001cited by this paper
• DNA Structure and Aspartate 276 Influence Nucleotide Binding to Human DNA Polymerase β

  2001cited by this paper
• Base excision repair in a network of defence and tolerance.

  2001cited by this paper
• Stimulation of human 8-oxoguanine-DNA glycosylase by AP-endonuclease: potential coordination of the initial steps in base excision repair.

  2001cited by this paper
• The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis.

  2000cited by this paper
• Substrate Specificity and Reaction Mechanism of Murine 8-Oxoguanine-DNA Glycosylase*

  2000cited by this paper
• Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice.

  2000cited by this paper
• Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases.

  2000cited by this paper
• Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA

  2000cited by this paper
• Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs.

  1999cited by this paper
• Spontaneous mutation, oxidative DNA damage, and the roles of base and nucleotide excision repair in the yeast Saccharomyces cerevisiae

  1999cited by this paper
• Single-turnover and pre-steady-state kinetics of the reaction of the adenine glycosylase MutY with mismatch-containing DNA substrates.

  1998cited by this paper
• Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA

  1998cited by this paper
• Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage.

  1998cited by this paper
• In search of a mutational hotspot.

  1998influential reference
• In vitro repair of oxidative DNA damage by human nucleotide excision repair system: possible explanation for neurodegeneration in xeroderma pigmentosum patients.

  1997cited by this paper
• Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community

  1997cited by this paper
• Substrate Binding by Human Apurinic/Apyrimidinic Endonuclease Indicates a Briggs-Haldane Mechanism*

  1997cited by this paper
• Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution*

  1997cited by this paper
• Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae.

  1997cited by this paper
• Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase.

  1997cited by this paper
• Specific Interaction of DNA Polymerase β and DNA Ligase I in a Multiprotein Base Excision Repair Complex from Bovine Testis*

  1996cited by this paper
• The Determination of Plasma Nitrite and Nitrate by Capillary Ion Analysis

  1995cited by this paper
• Base excision repair of U:G mismatches at a mutational hotspot in the p53 gene is more efficient than base excision repair of T:G mismatches in extracts of human colon tumors.

  1995cited by this paper
• Purification and domain-mapping of mammalian DNA polymerase beta.

  1995cited by this paper
• Gene number, noise reduction and biological complexity.

  1995cited by this paper
• DNA Polymerase Conducts the Gap-filling Step in Uracil-initiated Base Excision Repair in a Bovine Testis Nuclear Extract (*)

  1995cited by this paper
• [11] Purification and domain-mapping of mammalian DNA polymerase β

  1995cited by this paper
• Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers.

  1995cited by this paper
• The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA.

  1994cited by this paper
• Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer.

  1994cited by this paper
• Characterization of the effects of a thymine glycol residue on the structure, dynamics, and stability of duplex DNA by NMR.

  1993cited by this paper
• Number of CpG islands and genes in human and mouse.

  1993cited by this paper
• High frequency mutagenesis by a DNA methyltransferase.

  1992cited by this paper
• DNA base modifications in chromatin of human cancerous tissues

  1992cited by this paper
• THE P53 TUMOR SUPPRESSOR GENE

  1991cited by this paper
• The p53 tumour suppressor gene

  1991cited by this paper
• Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG

  1991cited by this paper
• DNA mismatch correction.

  1987influential reference
• Base stacking and molecular polarizability: effect of a methyl group in the 5-position of pyrimidines.

  1987cited by this paper
• DNA cytosine methylation and heat-induced deamination

  1986cited by this paper
• Dynamics of DNA duplexes containing internal G.T, G.A, A.C, and T.C pairs: hydrogen exchange at and adjacent to mismatch sites.

  1984influential reference
• Rare Bases in Animal DNA

  1970cited by this paper

• UVA-light-induced mutagenesis in the exome of human nucleotide excision repair-deficient cells

  2025cites this paper
• 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?

  2025cites this paper
• Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.

  2025cites this paper
• Direct Measurement of 8OG Syn-Anti Flips in Mutagenic 8OG·A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using 1H CEST NMR.

  2024cites this paper
• Oxidative stress accelerates intestinal tumorigenesis by enhancing 8-oxoguanine-mediated mutagenesis in MUTYH-deficient mice

  2024cites this paper
• Direct Measurement of 8OG syn-anti Flips in Mutagenic 8OG•A and Long-Range Damage-Dependent Hoogsteen Breathing Dynamics Using 1H CEST NMR

  2024cites this paper
• Endogenous Photosensitizers in Human Skin.

  2023cites this paper
• Complex Roles of NEIL1 and OGG1: Insights Gained from Murine Knockouts and Human Polymorphic Variants

  2022cites this paper
• DNA Sequence Modulates the Efficiency of NEIL1-Catalyzed Excision of the Aflatoxin B 1 -Induced Formamidopyrimidine (AFB 1 -Fapy) Guanine Adduct

  2022cites this paper
• Role of Small GTPase RhoA in DNA Damage Response

  2021cites this paper
• DNA Repair in Haploid Context

  2021cites this paper
• Molecular Mechanisms Associated with Clustered Lesion-Induced Impairment of 8-oxoG Recognition by the Human Glycosylase OGG1

  2021influential citation
• Mutagenicity Profile Induced by UVB Light in Human Xeroderma Pigmentosum Group C Cells †

  2021cites this paper
• Recognition of a tandem lesion by DNA bacterial formamidopyrimidine glycosylases explored combining molecular dynamics and machine learning

  2021cites this paper
• DNA Sequence Modulates the Efficiency of NEIL1-Catalyzed Excision of the Aflatoxin B1-Induced Formamidopyrimidine Guanine Adduct.

  2021cites this paper
• Recognition of a Tandem Lesion by DNA Glycosylases Explored Combining Molecular Dynamics and Machine Learning

  2021cites this paper
• Understanding the sequence and structural context effects in oxidative DNA damage repair.

  2020cites this paper
• The role of cysteines in the structure and function of OGG1

  2020cites this paper
• Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase

  2020cites this paper
• Current perspectives on mechanisms of ribonucleotide incorporation and processing in mammalian DNA

  2019cites this paper
• Eukaryotic Base Excision Repair: New Approaches Shine Light on Mechanism.

  2019cites this paper
• Shining light on the response to repair intermediates in DNA of living cells.

  2019cites this paper
• Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells

  2019cites this paper
• Apurinic/apyrimidinic (AP) endonuclease 1 processing of AP sites with 5' mismatches.

  2018cites this paper
• Human Oxoguanine Glycosylase 1 Removes Solution Accessible 8-Oxo-7,8-dihydroguanine Lesions from Globally Substituted Nucleosomes Except in the Dyad Region.

  2018cites this paper
• Expression and promoter methylation status of two DNA repair genes in leukocytes from patients undergoing propofol or isoflurane anaesthesia

  2018cites this paper
• Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA

  2018cites this paper
• DNA Base Excision Repair and Double Strand Break Repair in Human Fibroblast

  2017cites this paper
• Epigenetic Instability Induced by DNA Base Lesion via DNA Base Excision Repair

  2017cites this paper
• DNA Deformation-Coupled Recognition of 8-Oxoguanine: Conformational Kinetic Gating in Human DNA Glycosylase.

  2017cites this paper
• Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis

  2017cites this paper
• Differential Ability of Five DNA Glycosylases to Recognize and Repair Damage on Nucleosomal DNA.

  2017cites this paper
• Oxidized nucleotide insertion by pol β confounds ligation during base excision repair

  2017cites this paper
• AP endonuclease 1 prevents the extension of a T/G mismatch by DNA polymerase β to prevent mutations in CpGs during base excision repair.

  2016influential citation
• High-resolution Digital Mapping of N-Methylpurines in Human Cells Reveals Modulation of Their Induction and Repair by Nearest-neighbor Nucleotides*

  2015cites this paper
• Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome

  2015cites this paper
• Causes of genome instability: the effect of low dose chemical exposures in modern society.

  2015cites this paper
• Capturing Snapshots of APE1 Processing DNA Damage

  2015cites this paper
• The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic incision of abasic sites in DNA.

  2015cites this paper
• In Vivo DNA Repair Mechanisms and Carcinogenesis

  2014cites this paper
• Slow repair of lipid peroxidation-induced DNA damage at p53 mutation hotspots in human cells caused by low turnover of a DNA glycosylase

  2014cites this paper
• Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide*

  2014cites this paper
• 8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization.

  2014cites this paper
• Variations in brain DNA

  2014cites this paper
• Modulation of base excision repair of 8-oxoguanine by the nucleotide sequence

  2013cites this paper
• Excision of 8‐oxoguanine from methylated CpG dinucleotides by human 8‐oxoguanine DNA glycosylase

  2013cites this paper
• Roles of DNA Base Excision Repair in Maintaining the Integrity of DNA Methylation

  2013cites this paper
• Steady-state, pre-steady-state, and single-turnover kinetic measurement for DNA glycosylase activity.

  2013cites this paper
• Transient-state kinetics of apurinic/apyrimidinic (AP) endonuclease 1 acting on an authentic AP site and commonly used substrate analogs: the effect of diverse metal ions and base mismatches.

  2013cites this paper