ArticleNature chemistry2025
An unnatural base pair for the detection of epigenetic cytosine modifications in DNA.
Article in Nature chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A Universal Nucleoside-to-Nucleoside-5'-Triphosphate Enzyme Cascade Driven by Polyphosphate.Angewandte Chemie (International ed. in English) · 2026Article
- Programmable one-pot polymerase-mediated DNA synthesis via temperature control.Nature communications · 2026Article
- Synthesis and Incorporation of a pH-Responsive Nucleoside Into DNA Sequences.Chembiochem : a European journal of chemical biology · 2025Article
- An unnatural base pair for the detection of epigenetic cytosine modifications in DNA.Nature chemistry · 2025Article
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4 authors.
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Abstract
Natural, covalently modified cytosine bases within genomic DNA function as important epigenetic markers. Approaches for single-base-resolution sequencing of cytosine modifications typically deploy chemistry for modification-selective C-to-T code conversion and can require error-prone subtractive analysis of complex data. Here we report the sequencing of an epigenetic base by exploiting an unnatural base pair system. This approach relies on hydrogen-bonding complementarity between a malononitrile adduct of 5-formylcytosine and protonated 3,7-dideazaadenine. The specificity of this unnatural base pair was studied by biophysical DNA thermal melting analysis and by template-directed incorporation by DNA polymerase enzymes. Base pair selectivity was enhanced by controlling the protonation state of 3,7-dideazaadenine. We exemplify use of this unnatural base pair to sequence 5-formylcytosine in a DNA template using a Sanger-type format. There is scope for this base pair and the general concept to be implemented on further sequencing platforms that exploit Watson-Crick base pairing to directly identify epigenetic bases.
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