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

Linus F. Reichenbach, Ahmad Ahmad Sobri, Nathan R. Zaccai, Christopher Agnew, Nicholas Burton, Lucy P. Eperon, Sara de Ornellas, Ian C. Eperon, R. Leo. Brady, Glenn A. Burley

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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.
Original languageEnglish
Pages (from-to)946-958
Number of pages13
Issue number6
Publication statusPublished - 8 Dec 2016


  • synthetic biology
  • DNA
  • base pairs
  • mutation
  • synthetic base pairs
  • DNA structure
  • x-ray crystallography

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