Evidence map›Paper›PMID 26932196›Full record

ArticleNature communications2016

Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism.

Alain R Weber, Claudia Krawczyk, Adam B Robertson, Anna Kuśnierczyk, Cathrine B Vågbø, David Schuermann, Arne Klungland, Primo Schär

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
15.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 224 citations in OpenAlex.

  1. Article
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  4. mBiology direct · 2026
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  14. DNA Methylation in Rice: Mechanisms, Regulatory Roles, and Beyond.International journal of molecular sciences · 2025
    Review
  15. Article
  16. DNA polymerase β suppresses somatic indels at CpG dinucleotides in developing cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Article
  19. Review
  20. Article

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Alain R WeberDepartment of Biomedicine, University of Basel, Mattenstrasse 28, Basel CH-4058, Switzerland.
Claudia KrawczykDepartment of Biomedicine, University of Basel, Mattenstrasse 28, Basel CH-4058, Switzerland.
Adam B RobertsonDepartment of Molecular Microbiology, Oslo University Hospital, Rikshospitalet, NO-0372 Oslo, Norway.
Anna KuśnierczykProteomics and Metabolomics Core Facility, PROMEC, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.
Cathrine B VågbøProteomics and Metabolomics Core Facility, PROMEC, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway.
David SchuermannDepartment of Biomedicine, University of Basel, Mattenstrasse 28, Basel CH-4058, Switzerland.
Arne KlunglandDepartment of Molecular Microbiology, Oslo University Hospital, Rikshospitalet, NO-0372 Oslo, Norway.
Primo SchärDepartment of Biomedicine, University of Basel, Mattenstrasse 28, Basel CH-4058, Switzerland.
University of Basel · CHNorwegian University of Science and Technology · NOOslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytosine methylation in CpG dinucleotides is an epigenetic DNA modification dynamically established and maintained by DNA methyltransferases and demethylases. Molecular mechanisms of active DNA demethylation began to surface only recently with the discovery of the 5-methylcytosine (5mC)-directed hydroxylase and base excision activities of ten-eleven translocation (TET) proteins and thymine DNA glycosylase (TDG). This implicated a pathway operating through oxidation of 5mC by TET proteins, which generates substrates for TDG-dependent base excision repair (BER) that then replaces 5mC with C. Yet, direct evidence for a productive coupling of TET with BER has never been presented. Here we show that TET1 and TDG physically interact to oxidize and excise 5mC, and proof by biochemical reconstitution that the TET-TDG-BER system is capable of productive DNA demethylation. We show that the mechanism assures a sequential demethylation of symmetrically methylated CpGs, thereby avoiding DNA double-strand break formation but contributing to the mutability of methylated CpGs.

Indexed as

DNA MethylationCpG IslandsCytosineDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA RepairEpigenesis, GeneticEscherichia coliGene Expression RegulationProto-Oncogene ProteinsThymine DNA GlycosylaseCytosineDNA-Binding ProteinsProto-Oncogene ProteinsThymine DNA Glycosylase

Identifiers

PMID26932196
PMCPMC4778062
OpenAlexW2317132940

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.