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Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes
Open accessAbstract
Rare tautomeric and anionic nucleobases are believed to have fundamental biological roles, but their prevalence and functional importance has remained elusive because they exist transiently, in low abundance, and involve subtle movements of protons that are difficult to visualize. Using NMR relaxation dispersion, we show here that wobble dG•dT and rG•rU mispairs in DNA and RNA duplexes exist in dynamic equilibrium with short-lived, low-populated Watson-Crick-like mispairs that are stabilized by rare enolic or anionic bases. These mispairs can evade Watson-Crick fidelity checkpoints and form with probabilities (10(-3) to 10(-5)) that strongly imply a universal role in replication and translation errors. Our results indicate that rare tautomeric and anionic bases are widespread in nucleic acids, expanding their structural and functional complexity beyond that attainable with canonical bases.
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“More recently, tautomerisation in DNA has been experimentally observed using NMR relaxation dispersion.Here, hairpin DNA duplex structures were observed to interchange between a wobble G-T and a Watson-Crick-like structure via tautomerisation (neutral) or ionisation (charged) 9,51 .”
From An open quantum systems approach to proton tunnelling in DNA (2022) · cites this paper as [51]
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Metadata
- Authors
- Kimsey, I. J., Petzold, K., Sathyamoorthy, B., Stein, Z. W., & Al-Hashimi, H. M.
- Affiliations
- Duke University (US)
- Karolinska Institutet (SE)
- University of Michigan (US)
- Venue
- Nature
- Published
- 2015-03-11
- Volume
- 519
- Issue
- 7543
- Pages
- 315-320
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4547696
- OpenAlex
- W2066558081
- Cited by
- 261
- References
- 82
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 14 · 2023: 17 · 2022: 23 · 2021: 33 · 2020: 20 · 2019: 20 · 2018: 39 · 2017: 29 · 2016: 20 · 2015: 12
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM089846)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- tautomerism, enol tautomer, double-stranded DNA, RNA duplex, NMR relaxation dispersion, replication fidelity, translation errors
- MeSH terms
- Base Sequence, DNA, Hydrogen Bonding, Hydrogen-Ion Concentration, Mutation, Magnetic Resonance Spectroscopy, Nucleic Acid Heteroduplexes, Probability, RNA, DNA Fingerprinting, Base Pairing
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