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

Isaac J. Kimsey, Katja Petzold, Bharathwaj Sathyamoorthy, Zachary W. Stein and Hashim M. Al-Hashimi ()
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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

Nature, 2015, vol. 519, issue 7543, 315-320

Abstract: 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.

Date: 2015
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DOI: 10.1038/nature14227

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