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Nature. 2015 Mar 19;519(7543):315-20. doi: 10.1038/nature14227. Epub 2015 Mar 11.

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

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Department of Biochemistry and Chemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Biophysics, University of Michigan, Ann Arbor, Michigan 48109, USA.


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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