Structural basis of the mispairing of an artificially expanded genetic information system

Reichenbach, Linus F. and Sobri, Ahmad Ahmad and Zaccai, Nathan R. and Agnew, Christopher and Burton, Nicholas and Eperon, Lucy P. and de Ornellas, Sara and Eperon, Ian C. and Brady, R. Leo. and Burley, Glenn A. (2016) Structural basis of the mispairing of an artificially expanded genetic information system. Chem, 1 (6). pp. 946-958.

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    Abstract

    Relative to naturally occurring Watson-Crick base pairs, the synthetic nucleotide P pairs with Z within DNA duplexes through a unique hydrogen-bond arrangement. The loss of this synthetic genetic information by PCR results in the conversion of P-Z into a G-C base pair. Here, we show structural and spectroscopic evidence that the loss of this synthetic genetic information occurs via G-Z mispairing. Remarkably, the G-Z mispair is both plastic and pH dependent; it forms a double-hydrogen-bonded “slipped” pair at pH 7.8 and a triple-hydrogen-bonded Z-G pair when the pH is above 7.8. This study highlights the need for robust structural and functional methods to elucidate the mechanisms of mutation in the development of next-generation synthetic genetic base pairs.