ArticlePloS one2012
Highly mutagenic exocyclic DNA adducts are substrates for the human nucleotide incision repair pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Biochemical Effects of Natural and Nanoparticle Fish and Algal Oils in Gilt Pregnancy Diets on Base Excision Repair Enzymes in Newborn Piglets-Socioeconomic Implications for Regional Pig Farming-Preliminary Results.International journal of molecular sciences · 2025Article
- Administration of Natural Fish and Algal Oils in Nanoparticle Form to Pregnant Gilts and Newborn Piglets: Biochemical Effects and Spatial-Socio-Economic Implications for Regional Food Systems.International journal of molecular sciences · 2025Article
- The Trajectory of Damaged-Base Eversion into the Active Site of Apurinic/Apyrimidinic Endonuclease APE1 Regulates This Enzyme's Substrate Specificity.International journal of molecular sciences · 2024Article
- An Insight into the Mechanism of DNA Cleavage by DNA Endonuclease from the Hyperthermophilic ArchaeonInternational journal of molecular sciences · 2024Article
- Abasic site-peptide cross-links are blocking lesions repaired by AP endonucleases.Nucleic acids research · 2023Article
- Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans.Nucleic acids research · 2023Article
- Kinetic Features of 3'-5'-Exonuclease Activity of Apurinic/Apyrimidinic Endonuclease Apn2 fromInternational journal of molecular sciences · 2022Article
- Insights into Mechanisms of Damage Recognition and Catalysis by APE1-like Enzymes.International journal of molecular sciences · 2022Article
- Common Kinetic Mechanism of Abasic Site Recognition by Structurally Different Apurinic/Apyrimidinic Endonucleases.International journal of molecular sciences · 2021Article
- Regulation of GC box activity by 8-oxoguanine.Redox biology · 2021Article
- Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- The Role of Active-Site Plasticity in Damaged-Nucleotide Recognition by Human Apurinic/Apyrimidinic Endonuclease APE1.Molecules (Basel, Switzerland) · 2020Article
- Activity of Human Apurinic/Apyrimidinic Endonuclease APE1 Toward Damaged DNA and Native RNA With Non-canonical Structures.Frontiers in cell and developmental biology · 2020Article
- Substrate specificity of human apurinic/apyrimidinic endonuclease APE1 in the nucleotide incision repair pathway.Nucleic acids research · 2018Article
- Kinetic Features of 3'-5' Exonuclease Activity of Human AP-Endonuclease APE1.Molecules (Basel, Switzerland) · 2018Article
- The current state of eukaryotic DNA base damage and repair.Nucleic acids research · 2015Review
- Article
- Enzymatic MPG DNA repair assays for two different oxidative DNA lesions reveal associations with increased lung cancer risk.Carcinogenesis · 2014Article
- Uracil in duplex DNA is a substrate for the nucleotide incision repair pathway in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOxygen free radicals induce lipid peroxidation (LPO) that damages and breaks polyunsaturated fatty acids in cell membranes. LPO-derived aldehydes and hydroxyalkenals react with DNA leading to the formation of etheno(ε)-bases including 1,N(6)-ethenoadenine (εA) and 3,N(4)-ethenocytosine (εC). The εA and εC residues are highly mutagenic in mammalian cells and eliminated in the base excision repair (BER) pathway and/or by AlkB family proteins in the direct damage reversal process. BER initiated by DNA glycosylases is thought to be the major pathway for the removal of non-bulky endogenous base damage. Alternatively, in the nucleotide incision repair (NIR) pathway, the apurinic/apyrimidinic (AP) endonucleases can directly incise DNA duplex 5' to a damaged base in a DNA glycosylase-independent manner. METHODOLOGY/PRINCIPAL
findingsHere we have characterized the substrate specificity of human major AP endonuclease 1, APE1, towards εA, εC, thymine glycol (Tg) and 7,8-dihydro-8-oxoguanine (8oxoG) residues when present in duplex DNA. APE1 cleaves oligonucleotide duplexes containing εA, εC and Tg, but not those containing 8oxoG. Activity depends strongly on sequence context. The apparent kinetic parameters of the reactions suggest that APE1 has a high affinity for DNA containing ε-bases but cleaves DNA duplexes at an extremely slow rate. Consistent with this observation, oligonucleotide duplexes containing an ε-base strongly inhibit AP site nicking activity of APE1 with IC(50) values in the range of 5-10 nM. MALDI-TOF MS analysis of the reaction products demonstrated that APE1-catalyzed cleavage of εA•T and εC•G duplexes generates, as expected, DNA fragments containing 5'-terminal ε-base residue. CONCLUSIONS/SIGNIFICANCE: The fact that ε-bases and Tg in duplex DNA are recognized and cleaved by APE1 in vitro, suggests that NIR may act as a backup pathway to BER to remove a large variety of genotoxic base lesions in human cells.
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