Cited by 262DNA and Nucleic Acid ChemistryRNA and protein synthesis mechanismsProtein Structure and Dynamics

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Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes

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Kimsey, Isaac J., Petzold, Katja, Sathyamoorthy, Bharathwaj, Stein, Zachary W., Al-Hashimi, Hashim M.·2015·Nature

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Abstract

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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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)
ORCID: Petzold, Katja
Sathyamoorthy, Bharathwaj
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2015-03-11
Volume: 519
Issue: 7543
Pages: 315-320
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature14227
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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