ArticleNucleic acids research2012
Excision of 5-hydroxymethyluracil and 5-carboxylcytosine by the thymine DNA glycosylase domain: its structural basis and implications for active DNA demethylation.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 147 citations in OpenAlex.
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- Structural basis for uracil removal from DNA by human SMUG1.Nature communications · 2026Article
- Transcriptome remodeling of mouse hearts during postnatal cardiac maturation and under proteotoxic stress.Molecular biology reports · 2026Article
- Base-resolution profiling of 5-glyceryl-methylcytosine in Chlamydomonas reinhardtii via deaminase-assisted sequencing.Nucleic acids research · 2025Article
- Structure of a DNA Glycosylase Bound to a Nicked T:G Mismatch-Containing DNA.Molecules (Basel, Switzerland) · 2025Article
- The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.Epigenomics · 2025Review
- The role of DNA methylation and demethylation in bladder cancer: a focus on therapeutic strategies.Frontiers in oncology · 2025Review
- Quinoline-based compounds can inhibit diverse enzymes that act on DNA.Cell chemical biology · 2024Article
- Epigenetic DNA modifications and vitamin C in prostate cancer and benign prostatic hyperplasia: Exploring similarities, disparities, and pathogenic implications.Neoplasia (New York, N.Y.) · 2024Article
- Review
- Repair and DNA Polymerase Bypass of Clickable Pyrimidine Nucleotides.Biomolecules · 2024Article
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- How can we modulate aging through nutrition and physical exercise? An epigenetic approach.Aging · 2023Review
- Urinary Measurement of Epigenetic DNA Modifications and 8-oxodG as Possible Noninvasive Markers of Colon Cancer Evolution.International journal of molecular sciences · 2022Article
- Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer.Scientific reports · 2022Article
- FANCD2 maintains replication fork stability during misincorporation of the DNA demethylation products 5-hydroxymethyl-2'-deoxycytidine and 5-hydroxymethyl-2'-deoxyuridine.Cell death & disease · 2022Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- 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
- DNA Hydroxymethylation in Smoking-Associated Cancers.International journal of molecular sciences · 2022Review
- Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.Advances in experimental medicine and biology · 2022Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The mammalian thymine DNA glycosylase (TDG) is implicated in active DNA demethylation via the base excision repair pathway. TDG excises the mismatched base from G:X mismatches, where X is uracil, thymine or 5-hydroxymethyluracil (5hmU). These are, respectively, the deamination products of cytosine, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). In addition, TDG excises the Tet protein products 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) but not 5hmC and 5mC, when paired with a guanine. Here we present a post-reactive complex structure of the human TDG domain with a 28-base pair DNA containing a G:5hmU mismatch. TDG flips the target nucleotide from the double-stranded DNA, cleaves the N-glycosidic bond and leaves the C1' hydrolyzed abasic sugar in the flipped state. The cleaved 5hmU base remains in a binding pocket of the enzyme. TDG allows hydrogen-bonding interactions to both T/U-based (5hmU) and C-based (5caC) modifications, thus enabling its activity on a wider range of substrates. We further show that the TDG catalytic domain has higher activity for 5caC at a lower pH (5.5) as compared to the activities at higher pH (7.5 and 8.0) and that the structurally related Escherichia coli mismatch uracil glycosylase can excise 5caC as well. We discuss several possible mechanisms, including the amino-imino tautomerization of the substrate base that may explain how TDG discriminates against 5hmC and 5mC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.