ArticleNucleic acids research2014
Aberrant repair initiated by mismatch-specific thymine-DNA glycosylases provides a mechanism for the mutational bias observed in CpG islands.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- DNA Damage Recognition by Bacterial and Human Adenine-DNA Glycosylases: Insights from Non-Canonical Substrates.Biomolecules · 2026Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Nature communications · 2026Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Research square · 2025Article
- CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- 8-Oxoadenine: A «New» Player of the Oxidative Stress in Mammals?International journal of molecular sciences · 2024Review
- Enhanced thermal stability enables human mismatch-specific thymine-DNA glycosylase to catalyse futile DNA repair.PloS one · 2024Article
- The Role of Thymine DNA Glycosylase in Transcription, Active DNA Demethylation, and Cancer.Cancers · 2022Review
- DNA Sequence Modulates the Efficiency of NEIL1-Catalyzed Excision of the Aflatoxin BChemical research in toxicology · 2021Article
- Role of Base Excision Repair Pathway in the Processing of Complex DNA Damage Generated by Oxidative Stress and Anticancer Drugs.Frontiers in cell and developmental biology · 2020Review
- Mutagenic Replication of the Major Oxidative Adenine Lesion 7,8-Dihydro-8-oxoadenine by Human DNA Polymerases.Journal of the American Chemical Society · 2019Article
- Aberrant repair initiated by the adenine-DNA glycosylase does not play a role in UV-induced mutagenesis inPeerJ · 2018Article
- Oligodeoxynucleotides Can Transiently Up- and Downregulate CHS Gene Expression in Flax by Changing DNA Methylation in a Sequence-Specific Manner.Frontiers in plant science · 2017Article
- Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis.Acta biochimica et biophysica Sinica · 2016Review
- Breaking bad: The mutagenic effect of DNA repair.DNA repair · 2015Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human thymine-DNA glycosylase (TDG) initiates the base excision repair (BER) pathway to remove spontaneous and induced DNA base damage. It was first biochemically characterized for its ability to remove T mispaired with G in CpG context. TDG is involved in the epigenetic regulation of gene expressions by protecting CpG-rich promoters from de novo DNA methylation. Here we demonstrate that TDG initiates aberrant repair by excising T when it is paired with a damaged adenine residue in DNA duplex. TDG targets the non-damaged DNA strand and efficiently excises T opposite of hypoxanthine (Hx), 1,N(6)-ethenoadenine, 7,8-dihydro-8-oxoadenine and abasic site in TpG/CpX context, where X is a modified residue. In vitro reconstitution of BER with duplex DNA containing Hx•T pair and TDG results in incorporation of cytosine across Hx. Furthermore, analysis of the mutation spectra inferred from single nucleotide polymorphisms in human population revealed a highly biased mutation pattern within CpG islands (CGIs), with enhanced mutation rate at CpA and TpG sites. These findings demonstrate that under experimental conditions used TDG catalyzes sequence context-dependent aberrant removal of thymine, which results in TpG, CpA→CpG mutations, thus providing a plausible mechanism for the putative evolutionary origin of the CGIs in mammalian genomes.
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