ArticleACS chemical biology2016
Weakened N3 Hydrogen Bonding by 5-Formylcytosine and 5-Carboxylcytosine Reduces Their Base-Pairing Stability.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 62 citations in OpenAlex.
- Computational Prediction of One-Electron Oxidation Potentials for Cytosine and Uracil Epigenetic Derivatives.The journal of physical chemistry. A · 2025Article
- Kinetics and dynamics of oligonucleotide hybridization.Nature reviews. Chemistry · 2025Review
- The photoactivated dynamics of dGpdC and dCpdG sequences in DNA: a comprehensive quantum mechanical study.Chemical science · 2024Article
- A Photoredox Reaction for the Selective Modification of 5-Carboxycytosine in DNA.Journal of the American Chemical Society · 2023Article
- Article
- Cytosine base modifications regulate DNA duplex stability and metabolism.Nucleic acids research · 2021Article
- Interaction of Thymine DNA Glycosylase with Oxidised 5-Methyl-cytosines in Their Amino- and Imino-Forms.Molecules (Basel, Switzerland) · 2021Article
- The epigenetic DNA modification 5-carboxylcytosine promotes high levels of cyclobutane pyrimidine dimer formation upon UVB irradiation.Genome instability & disease · 2021Article
- Structural dynamics of double-stranded DNA with epigenome modification.Nucleic acids research · 2021Article
- Impact of 5-formylcytosine on the melting kinetics of DNA by 1H NMR chemical exchange.Nucleic acids research · 2020Article
- Epigenetic TET-Catalyzed Oxidative Products of 5-Methylcytosine Impede Z-DNA Formation of CG Decamers.ACS omega · 2020Article
- Modeling the vibrational couplings of nucleobases.The Journal of chemical physics · 2020Article
- Oxidized Derivatives of 5-Methylcytosine Alter the Stability and Dehybridization Dynamics of Duplex DNA.The journal of physical chemistry. B · 2020Article
- 5-Carboxylcytosine and Cytosine Protonation Distinctly Alter the Stability and Dehybridization Dynamics of the DNA Duplex.The journal of physical chemistry. B · 2020Article
- Epigenetic modification of cytosines fine tunes the stability of i-motif DNA.Nucleic acids research · 2020Article
- Site- and degree-specific C-H oxidation on 5-methylcytosine homologues for probing active DNA demethylation.Chemical science · 2019Article
- Excision of 5-Carboxylcytosine by Thymine DNA Glycosylase.Journal of the American Chemical Society · 2019Article
- TET-Catalyzed 5-Carboxylcytosine Promotes CTCF Binding to Suboptimal Sequences Genome-wide.iScience · 2019Article
- Development of Vibrational Frequency Maps for Nucleobases.The journal of physical chemistry. B · 2019Article
- Molecular basis for the faithful replication of 5-methylcytosine and its oxidized forms by DNA polymerase β.The Journal of biological chemistry · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In the active cytosine demethylation pathway, 5-methylcytosine (5mC) is oxidized sequentially to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Thymine DNA glycosylase (TDG) selectively excises 5fC and 5caC but not cytosine (C), 5mC, and 5hmC. We propose that the electron-withdrawing properties of -CHO and -COOH in 5fC and 5caC increase N3 acidity, leading to weakened hydrogen bonding and reduced base pair stability relative to C, 5mC, and 5hmC, thereby facilitating the selective recognition of 5fC and 5caC by TDG. Through (13)C NMR, we measured the pKa at N3 of 5fC as 2.4 and the two pKa's of 5caC as 2.1 and 4.2. We used isotope-edited IR spectroscopy coupled with density functional theory (DFT) calculations to site-specifically assign the more acidic pKa of 5caC to protonation at N3, indicating that N3 acidity is increased in 5fC and 5caC relative to C. IR and UV melting studies of self-complementary DNA oligomers confirm reduced stability for 5fC-G and 5caC-G base pairs. Furthermore, while the 5fC-G base pair stability is insensitive to pH, the 5caC-G stability is reduced as pH decreases and the carboxyl group is increasingly protonated. Despite suggestions that 5fC and 5caC may exist in rare tautomeric structures which form wobble GC base pairs, our two-dimensional infrared (2D IR) spectroscopy of 5fC and 5caC free nucleosides confirms that both bases are predominantly in the canonical amino-keto form. Taken together, these findings support our model that weakened base pairing ability for 5fC and 5caC in dsDNA contributes to their selective recognition by TDG.
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