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

Author

Listed:
  • Isaac J. Kimsey

    (Duke University Medical Center)

  • Katja Petzold

    (Karolinska Institute, SE-171 77 Stockholm, Sweden)

  • Bharathwaj Sathyamoorthy

    (Duke University Medical Center)

  • Zachary W. Stein

    (Biophysics, University of Michigan, Ann Arbor, Michigan 48109, USA)

  • Hashim M. Al-Hashimi

    (Duke University Medical Center)

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.

Suggested Citation

  • Isaac J. Kimsey & Katja Petzold & Bharathwaj Sathyamoorthy & Zachary W. Stein & Hashim M. Al-Hashimi, 2015. "Visualizing transient Watson–Crick-like mispairs in DNA and RNA duplexes," Nature, Nature, vol. 519(7543), pages 315-320, March.
    • Handle: RePEc:nat:nature:v:519:y:2015:i:7543:d:10.1038_nature14227
    DOI: 10.1038/nature14227
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    Cited by:

    1. Qun Tang & Mitchell Gulkis & Robert McKenna & Melike Çağlayan, 2022. "Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Joonas A. Jamsen & David D. Shock & Samuel H. Wilson, 2022. "Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Ge Han & Yi Xue, 2022. "Rational design of hairpin RNA excited states reveals multi-step transitions," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Ainan Geng & Laura Ganser & Rohit Roy & Honglue Shi & Supriya Pratihar & David A. Case & Hashim M. Al-Hashimi, 2023. "An RNA excited conformational state at atomic resolution," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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