ArticleJournal of the American Chemical Society2019
Excision of 5-Carboxylcytosine by Thymine DNA Glycosylase.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Robust excision of different purine lesions by homologs thymine DNA glycosylase and mismatch-specific uracil DNA-glycosylase.The Journal of biological chemistry · 2026Article
- Positive TAZ-TDG feedback loop drives proneural-to-mesenchymal transition to promote glioblastoma progression.Journal of translational medicine · 2026Article
- Thymine DNA glycosylase binds to R-loops and excises 5-formyl and 5-carboxyl cytosine from DNA/RNA hybrids.The Journal of biological chemistry · 2026Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Observing nucleotide flipping in DNA using indirect 2'-F nucleotide probes and 19F NMR.Nucleic acids research · 2025Article
- Review
- Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine.Nature communications · 2024Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.Advances in experimental medicine and biology · 2022Article
- DNA Methyltransferases and DNA Damage.Advances in experimental medicine and biology · 2022Article
- Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming.PloS one · 2022Article
- The base excision repair process: comparison between higher and lower eukaryotes.Cellular and molecular life sciences : CMLS · 2021Review
- Intragenomic Decarboxylation of 5-Carboxy-2'-deoxycytidine.Angewandte Chemie (International ed. in English) · 2021Article
- Interaction of Thymine DNA Glycosylase with Oxidised 5-Methyl-cytosines in Their Amino- and Imino-Forms.Molecules (Basel, Switzerland) · 2021Article
- Structural Insights into the Mechanism of Base Excision by MBD4.Journal of molecular biology · 2021Article
- 5-Hydroxymethyl-, 5-Formyl- and 5-Carboxydeoxycytidines as Oxidative Lesions and Epigenetic Marks.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- TET-TDG Active DNA Demethylation at CpG and Non-CpG Sites.Journal of molecular biology · 2021Article
- Atomic resolution of short-range sliding dynamics of thymine DNA glycosylase along DNA minor-groove for lesion recognition.Nucleic acids research · 2021Article
- Oxidized Derivatives of 5-Methylcytosine Alter the Stability and Dehybridization Dynamics of Duplex DNA.The journal of physical chemistry. B · 2020Article
- 5-Carboxylcytosine and Cytosine Protonation Distinctly Alter the Stability and Dehybridization Dynamics of the DNA Duplex.The journal of physical chemistry. B · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
5-Methylcytosine (mC) is an epigenetic mark that is written by methyltransferases, erased through passive and active mechanisms, and impacts transcription, development, diseases including cancer, and aging. Active DNA demethylation involves TET-mediated stepwise oxidation of mC to 5-hydroxymethylcytosine, 5-formylcytosine (fC), or 5-carboxylcytosine (caC), excision of fC or caC by thymine DNA glycosylase (TDG), and subsequent base excision repair. Many elements of this essential process are poorly defined, including TDG excision of caC. To address this problem, we solved high-resolution structures of human TDG bound to DNA with cadC (5-carboxyl-2'-deoxycytidine) flipped into its active site. The structures unveil detailed enzyme-substrate interactions that mediate recognition and removal of caC, many involving water molecules. Importantly, two water molecules contact a carboxylate oxygen of caC and are poised to facilitate acid-catalyzed caC excision. Moreover, a substrate-dependent conformational change in TDG modulates the hydrogen bond interactions for one of these waters, enabling productive interaction with caC. An Asn residue (N191) that is critical for caC excision is found to contact N3 and N4 of caC, suggesting a mechanism for acid-catalyzed base excision that features an N3-protonated form of caC but would be ineffective for C, mC, or hmC. We also investigated another Asn residue (N140) that is catalytically essential and strictly conserved in the TDG-MUG enzyme family. A structure of N140A-TDG bound to cadC DNA provides the first high-resolution insight into how enzyme-substrate interactions, including water molecules, are impacted by depleting the conserved Asn, informing its role in binding and addition of the nucleophilic water molecule.
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Registered trials
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.