ArticleProceedings of the National Academy of Sciences of the United States of America2013
Uracil in duplex DNA is a substrate for the nucleotide incision repair pathway in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 76 citations in OpenAlex.
- TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity.Nature communications · 2026Article
- 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
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- An Insight into the Mechanism of DNA Cleavage by DNA Endonuclease from the Hyperthermophilic ArchaeonInternational journal of molecular sciences · 2024Article
- Research on the influence of APOBEC family on the occurrence, diagnosis, and treatment of various tumors.Journal of cancer research and clinical oncology · 2023Review
- Kinetic Features of 3'-5'-Exonuclease Activity of Apurinic/Apyrimidinic Endonuclease Apn2 fromInternational journal of molecular sciences · 2022Article
- Differential ETS1 binding to T:G mismatches within a CpG dinucleotide contributes to C-to-T somatic mutation rate of the IDH2 hotspot at codon Arg140.DNA repair · 2022Article
- Base excision-initiated terminal deoxynucleotide transferase-assisted amplification for simultaneous detection of multiple DNA glycosylases.Analytical and bioanalytical chemistry · 2022Article
- Uracil-DNA Glycosylase Assay by Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry Analysis.Journal of visualized experiments : JoVE · 2022Article
- Insights into Mechanisms of Damage Recognition and Catalysis by APE1-like Enzymes.International journal of molecular sciences · 2022Article
- Comparative Analysis of Exo- and Endonuclease Activities of APE1-like Enzymes.International journal of molecular sciences · 2022Article
- Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.Nature methods · 2021Article
- Common Kinetic Mechanism of Abasic Site Recognition by Structurally Different Apurinic/Apyrimidinic Endonucleases.International journal of molecular sciences · 2021Article
- Review
- The Enigma of Substrate Recognition and Catalytic Efficiency of APE1-Like Enzymes.Frontiers in cell and developmental biology · 2021Article
- Intrinsic Strand-Incision Activity of Human UNG: Implications for Nick Generation in Immunoglobulin Gene Diversification.Frontiers in immunology · 2021Article
- Base excision repair and its implications to cancer therapy.Essays in biochemistry · 2020Review
- The Role of Active-Site Plasticity in Damaged-Nucleotide Recognition by Human Apurinic/Apyrimidinic Endonuclease APE1.Molecules (Basel, Switzerland) · 2020Article
- Molecular Basis of Substrate Recognition of Endonuclease Q from the Euryarchaeon Pyrococcus furiosus.Journal of bacteriology · 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
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8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spontaneous hydrolytic deamination of cytosine to uracil (U) in DNA is a constant source of genome instability in cells. This mutagenic process is greatly enhanced at high temperatures and in single-stranded DNA. If not repaired, these uracil residues give rise to C → T transitions, which are the most common spontaneous mutations occurring in living organisms and are frequently found in human tumors. In the majority of species, uracil residues are removed from DNA by specific uracil-DNA glycosylases in the base excision repair pathway. Alternatively, in certain archaeal organisms, uracil residues are eliminated by apurinic/apyrimidinic (AP) endonucleases in the nucleotide incision repair pathway. Here, we characterized the substrate specificity of the major human AP endonuclease 1, APE1, toward U in duplex DNA. APE1 cleaves oligonucleotide duplexes containing a single U⋅G base pair; this activity depends strongly on the sequence context and the base opposite to U. The apparent kinetic parameters of the reactions show that APE1 has high affinity for DNA containing U but cleaves the DNA duplex at an extremely low rate. MALDI-TOF MS analysis of the reaction products demonstrated that APE1-catalyzed cleavage of a U⋅G duplex generates the expected DNA fragments containing a 5'-terminal deoxyuridine monophosphate. The fact that U in duplex DNA is recognized and cleaved by APE1 in vitro suggests that this property of the exonuclease III family of AP endonucleases is remarkably conserved from Archaea to humans. We propose that nucleotide incision repair may act as a backup pathway to base excision repair to remove uracils arising from cytosine deamination.
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