ArticleThe Journal of biological chemistry2011
Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 476 papers.
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Who cites it
476 citing papers in PubMed, 807 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies: DNA methylation in pancreatic cancer.Cancer biology & therapy · 2026Review
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Robust excision of different purine lesions by homologs thymine DNA glycosylase and mismatch-specific uracil DNA-glycosylase.The Journal of biological chemistry · 2026Article
- Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers.Nature chemical biology · 2026Article
- Changes in active DNA demethylation pathway components during neoadjuvant chemotherapy and their prognostic significance in breast cancer.Breast cancer research : BCR · 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
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell fate acquisition.Nucleic acids research · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- Epigenetic regulation in transplant rejection and tolerance: mechanisms and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- 5-Hydroxymethylcytosine: a key epigenetic mark in cancer and chemotherapy response.Epigenetics & chromatin · 2025Review
- An unnatural base pair for the detection of epigenetic cytosine modifications in DNA.Nature chemistry · 2025Article
- Steroid hormone-mediated epigenetic programming during puberty: uncovering links to depression.Epigenomics · 2025Review
- Epigenetic control of cell identities from epiblast to gastrulation.The FEBS journal · 2025Review
- DNA Methylation in Rice: Mechanisms, Regulatory Roles, and Beyond.International journal of molecular sciences · 2025Review
- Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.Nucleic acids research · 2025Review
- DNA glycosylases Ogg1 and Mutyh influence gene expression of PRC2 targets associated with cognition.Cellular and molecular life sciences : CMLS · 2025Article
- Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development.PLoS biology · 2025Article
416 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Thymine DNA glycosylase (TDG) excises T from G·T mispairs and is thought to initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent studies show that TDG, including its glycosylase activity, is essential for active DNA demethylation and embryonic development. These and other findings suggest that active demethylation could involve mC deamination by a deaminase, giving a G·T mispair followed by TDG-initiated BER. An alternative proposal is that demethylation could involve iterative oxidation of mC to 5-hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5-carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with conversion of caC to C by a putative decarboxylase. Our previous studies suggest that TDG could excise fC and caC from DNA, which could provide another potential demethylation mechanism. We show here that TDG rapidly removes fC, with higher activity than for G·T mispairs, and has substantial caC excision activity, yet it cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is consistent with its strong specificity for excising bases from a CpG context. Our findings reveal a remarkable new aspect of specificity for TDG, inform its catalytic mechanism, and suggest that TDG could protect against fC-induced mutagenesis. The results also suggest a new potential mechanism for active DNA demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent BER. Such a mechanism obviates the need for a decarboxylase and is consistent with findings that TDG glycosylase activity is essential for active demethylation and embryonic development, as are mechanisms involving TDG excision of deaminated mC or hmC.
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