The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., & Zhang, Y. (2011) · Science · doi:10.1126/science.1210597 · Cited by 3,451
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700
Cited by
TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661
TET enzymes, TDG and the dynamics of DNA demethylation
Kohli, R. M., & Zhang, Y. (2013) · Nature · doi:10.1038/nature12750 · Cited by 1,623
Role of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
Wu, H., & Zhang, Y. (2014) · Cell · doi:10.1016/j.cell.2013.12.019 · Cited by 1,065
“While TDG cannot efficiently remove 5mC or 5hmC, it exhibits robust in vitro excision activity toward 5fC or 5caC (5fC,G or 5caC,G pairs) in duplex DNA (He et al., 2011; Maiti and Drohat, 2011).”
InfluentialDynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.004 · Cited by 973
TETonic shift: biological roles of TET proteins in DNA demethylation and transcription
Pastor, W. A., Aravind, L., & Rao, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3589 · Cited by 897
Uncovering the role of 5-hydroxymethylcytosine in the epigenome
Branco, M. R., Ficz, G., & Reik, W. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3080 · Cited by 766
Transcription factors as readers and effectors of DNA methylation
Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649
Yin, R., Mao, S.-Q., Zhao, B., Chong, Z., Yang, Y., Zhao, C., Zhang, D., Huang, H., Gao, J., Li, Z., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4028346 · Cited by 609
Genome-wide Analysis Reveals TET- and TDG-Dependent 5-Methylcytosine Oxidation Dynamics
Shen, L., Wu, H., Diep, D., Yamaguchi, S., D’Alessio, A. C., Fung, H.-L., Zhang, K., & Zhang, Y. (2013) · Cell · doi:10.1016/j.cell.2013.04.002 · Cited by 497
DNA methylation: An epigenetic mark of cellular memory
Kim, M., & Costello, J. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.10 · Cited by 450
DNA glycosylases: In DNA repair and beyond
Jacobs, A. L., & Schär, P. (2012) · Chromosoma · doi:10.1007/s00412-011-0347-4 · Cited by 407
Tet-Mediated Formation of 5-Hydroxymethylcytosine in RNA
Fu, L., Guerrero, C. R., Zhong, N., Amato, N. J., Liu, Y., Liu, S., Cai, Q., Ji, D., Jin, S.-G., Niedernhofer, L. J., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505305z · Cited by 404
Regulation of the epigenome by vitamin C
Young, J. I., Züchner, S., & Wang, G. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034228 · Cited by 319
Kinde, B., Gabel, H. W., Gilbert, C. S., Griffith, E. C., & Greenberg, M. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411269112 · Cited by 236
DNA Repair by Reversal of DNA Damage
Yi, C., & He, C. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012575 · Cited by 161
Potential functional roles of DNA demethylation intermediates
Song, C.-X., & He, C. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.07.003 · Cited by 154
Jin, S.-G., Zhang, Z.-M., Dunwell, T. L., Harter, M. R., Wu, X., Johnson, J., Li, Z., Liu, J., Szabó, P. E., Lu, Q., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.044 · Cited by 138
Tet Enzymes, Variants, and Differential Effects on Function
Melamed, P., Yosefzon, Y., David, C., Tsukerman, A., & Pnueli, L. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00022 · Cited by 130
Kang, J., Lienhard, M., Pastor, W. A., Chawla, A., Novotny, M., Tsagaratou, A., Lasken, R. S., Thompson, E. C., Surani, M. A., Koralov, S. B., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510510112 · Cited by 126
Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells
Pan, F., Wingo, T. S., Zhao, Z., Gao, R., Makishima, H., Qu, G., Lin, L., Yu, M., Ortega, J. R., Wang, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms15102 · Cited by 117
Gabriele, M., Lopez Tobon, A., D'Agostino, G., & Testa, G. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.12.013 · Cited by 103
TET2 in Normal and Malignant Hematopoiesis
Bowman, R. L., & Levine, R. L. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026518 · Cited by 94
DNA damage and transcription stress
Milano, L., Gautam, A., & Caldecott, K. W. (2024) · Molecular Cell · doi:10.1016/j.molcel.2023.11.014 · Cited by 88
Suzuki, T., Shimizu, Y., Furuhata, E., Maeda, S., Kishima, M., Nishimura, H., Enomoto, S., Hayashizaki, Y., & Suzuki, H. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017005710 · Cited by 87
Human Papillomavirus 16 E5 Inhibits Interferon Signaling and Supports Episomal Viral Maintenance
Scott, M. L., Woodby, B. L., Ulicny, J., Raikhy, G., Orr, A. W., Songock, W. K., & Bodily, J. M. (2020) · Journal of Virology · doi:10.1128/jvi.01582-19 · Cited by 87
Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine
Liu, M. Y., Torabifard, H., Crawford, D. J., DeNizio, J. E., Cao, X.-J., Garcia, B. A., Cisneros, G. A., & Kohli, R. M. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2250 · Cited by 78
Clonal hematopoiesis and hematological malignancy
Dunn, W. G., McLoughlin, M. A., & Vassiliou, G. S. (2024) · Journal of Clinical Investigation · doi:10.1172/jci180065 · Cited by 61
Decoding the role of TET family dioxygenases in lineage specification
Wu, X., Li, G., & Xie, R. (2018) · Epigenetics & Chromatin · doi:10.1186/s13072-018-0228-7 · Cited by 43
Epigenetic signature in neural plasticity: the journey so far and journey ahead
Nayak, M., Das, D., Pradhan, J., Ahmed, R. G., Laureano-Melo, R., & Dandapat, J. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e12292 · Cited by 42
TET-TDG active DNA demethylation at CpG and non-CpG sites
DeNizio, J. E., Dow, B. J., Serrano, J. C., Ghanty, U., Drohat, A. C., & Kohli, R. M. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166877 · Cited by 32
Perinatal stress and epigenetics.
(2021) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-820107-7.00008-2 · Cited by 28
Metadata
- Authors
- Maiti, A., & Drohat, A. C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 286
- Issue
- 41
- Pages
- 35334-35338
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2129270269
- Cited by
- 828
- References
- 2
- FWCI
- 26.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
