ArticleNature chemical biology2012
AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers, 1 of them a synthesis that pooled it.
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Who cites it
176 citing papers in PubMed, 1 synthesis or guideline pooled it, 301 citations in OpenAlex.
- Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.Frontiers in immunology · 2021Pooled it
- 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
- Spatially concentrated adenine base editors efficiently correct PLP1 mutations in oligodendrocytes.Nucleic acids research · 2026Article
- Metformin-mediated modulation of epigenetic regulators in type 2 diabetes: A study on differential expression of DNMT1, TET1, OGG1, and AID genes.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Impact of sperm fractionation on chromosome positioning, chromatin integrity, DNA methylation, and hydroxymethylation level.Cellular & molecular biology letters · 2025Article
- What is in a name? Rethinking SMUG1 in genome maintenance.NAR cancer · 2025Review
- DNA methylation biomarkers for the diagnosis and treatment management of breast cancer: where are we now?Epigenomics · 2025Review
- The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025Review
- Review
- Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DNA methylation and demethylation in adipocyte biology: roles of DNMT and TET proteins in metabolic disorders.Frontiers in endocrinology · 2025Review
- Impact of Short-Term Exposure to Non-Functionalized Polystyrene Nanoparticles on DNA Methylation and Gene Expression in Human Peripheral Blood Mononuclear Cells.International journal of molecular sciences · 2024Article
- 5-Hydroxymethylcytosine: Far Beyond the Intermediate of DNA Demethylation.International journal of molecular sciences · 2024Review
- Review
- Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects.Nature biotechnology · 2024Article
- APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Engineered deaminases as a key component of DNA and RNA editing tools.Molecular therapy. Nucleic acids · 2023Review
- Direct enzymatic sequencing of 5-methylcytosine at single-base resolution.Nature chemical biology · 2023Article
116 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Activation-induced deaminase (AID)/APOBEC-family cytosine deaminases, known to function in diverse cellular processes from antibody diversification to mRNA editing, have also been implicated in DNA demethylation, a major process for transcriptional activation. Although oxidation-dependent pathways for demethylation have been described, pathways involving deamination of either 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) have emerged as alternatives. Here we address the biochemical plausibility of deamination-coupled demethylation. We found that purified AID/APOBECs have substantially reduced activity on 5mC relative to cytosine, their canonical substrate, and no detectable deamination of 5hmC. This finding was explained by the reactivity of a series of modified substrates, where steric bulk was increasingly detrimental to deamination. Further, upon AID/APOBEC overexpression, the deamination product of 5hmC was undetectable in genomic DNA, whereas oxidation intermediates remained detectable. Our results indicate that the steric requirements for cytosine deamination are one intrinsic barrier to the proposed function of deaminases in DNA demethylation.
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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.