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Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System

DOI: 10.1016/j.chempr.2016.11.009 DOI Help

Authors: Linus F. Reichenbach (University of Strathclyde) , Ahmad Ahmad Sobri (University of Bristol) , Nathan R. Zaccai (University of Bristol) , Christopher Agnew (University of Bristol) , Nicholas Burton (University of Bristol) , Lucy P. Eperon (University of Leicester) , Sara De Ornellas (University of Strathclyde) , Ian C. Eperon (University of Leicester) , R. Leo Brady (University of Bristol) , Glenn A. Burley (University of Strathclyde)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chem , VOL 1 , PAGES 946 - 958

State: Published (Approved)
Published: December 2016
Diamond Proposal Number(s): 8922 , 12342

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.

Journal Keywords: synthetic biology; DNA; base pairs; mutation; PCR; synthetic base pairs; DNA structure; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

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