ArticleNucleic acids research1997
The Ogg1 protein of Saccharomyces cerevisiae: a 7,8-dihydro-8-oxoguanine DNA glycosylase/AP lyase whose lysine 241 is a critical residue for catalytic activity.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 125 citations in OpenAlex.
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- TORC2 inhibition triggers yeast chromosome fragmentation through misregulated Base Excision Repair of clustered oxidation events.Nature communications · 2024Article
- DNA adduct formation in Saccharomyces cerevisiae following exposure to environmental pollutants, as in vivo model for molecular toxicity studies.World journal of microbiology & biotechnology · 2024Article
- A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophilus Ch5 is a new member of AGOG DNA glycosylase familyActa biochimica et biophysica Sinica · 2022Article
- DNA-Protein Cross-Linking Sequencing for Genome-Wide Mapping of Thymidine Glycol.Journal of the American Chemical Society · 2022Article
- DNA Repair in Haploid Context.International journal of molecular sciences · 2021Review
- Dynamic Processing of a Common Oxidative DNA Lesion by the First Two Enzymes of the Base Excision Repair Pathway.Journal of molecular biology · 2021Article
- Oxidative DNA-protein crosslinks formed in mammalian cells by abasic site lyases involved in DNA repair.DNA repair · 2020Article
- Apurinic/Apyrimidinic Endonuclease 1 and Tyrosyl-DNA Phosphodiesterase 1 Prevent Suicidal Covalent DNA-Protein Crosslink at Apurinic/Apyrimidinic Site.Frontiers in cell and developmental biology · 2020Article
- The regulatory G4 motif of the Kirsten ras (KRAS) gene is sensitive to guanine oxidation: implications on transcription.Nucleic acids research · 2018Article
- AP-Endonuclease 1 Accelerates Turnover of Human 8-Oxoguanine DNA Glycosylase by Preventing Retrograde Binding to the Abasic-Site Product.Biochemistry · 2017Article
- Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.Molecular cancer research : MCR · 2016Article
- The current state of eukaryotic DNA base damage and repair.Nucleic acids research · 2015Review
- In Vitro Fluorogenic Real-Time Assay of the Repair of Oxidative DNA Damage.Chembiochem : a European journal of chemical biology · 2015Article
- Review
- In vivo bypass of 8-oxodG.PLoS genetics · 2013Article
- Alkylation base damage is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease.PLoS genetics · 2011Article
- Variant base excision repair proteins: contributors to genomic instability.Seminars in cancer biology · 2010Review
- Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.Nucleic acids research · 2009Article
- PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae.Nucleic acids research · 2009Article
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3 authors at 1 institution in 1 country.
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Abstract
The OGG1 gene of Saccharomyces cerevisiae codes for a DNA glycosylase that excises 7,8-dihydro-8- oxoguanine (8-OxoG) and 2,6-diamino-4-hydroxy-5- N -methylformamidopyrimidine (Fapy) from damaged DNA. In this paper, we have analysed the substrate specificity and the catalytic mechanism of the Ogg1 protein acting on DNA subtrates containing 8-OxoG residues or apurinic/apyrimidinic (AP) sites. The Ogg1 protein displays a marked preference for DNA duplexes containing 8-OxoG placed opposite a cytosine, the rank order for excision of 8-OxoG and cleavage efficiencies being 8-OxoG/C >8-OxoG/T >>8-OxoG/G and 8-OxoG/A. The cleavage of the DNA strand implies the excision of 8-OxoG followed by abeta-elimination reaction at the 3'-side of the resulting AP site. The Ogg1 protein efficiently cleaves a DNA duplex where a preformed AP site is placed opposite a cytosine (AP/C). In contrast, AP/T, AP/A or AP/G substrates are incised with a very low efficiency. Furthermore, cleavage of 8-OxoG/C or AP/C substrates implies the formation of a reaction intermediate that is converted into a stable covalent adduct in the presence of sodium borohydre (NaBH4). Therefore, the Ogg1 protein is a eukaryotic DNA glycosylase/AP lyase. Sequence homology searches reveal that Ogg1 probably shares a common ancestor gene with the endonuclease III of Escherichia coli. A consensus sequence indicates a highly conserved lysine residue, K120 of endonuclease III or K241 of Ogg1, respectively. Mutations of K241 to Gln (K241Q) and Arg (K241R) have been obtained after site directed mutagenesis of OGG1. Mutation K241Q completely abolishes DNA glycosylase activity and covalent complex formation in the presence of NaBH4. However, the K241Q mutant still binds DNA duplexes containing 8-OxoG/C. In contrast, K241R mutation results in a catalytically active form of Ogg1. These results strongly suggest that the free amino group of Lys241 is involved in the catalytic mechanism of the Ogg1 protein.
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