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

Research output: Contribution to journalArticle

  • 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
Original languageEnglish
Pages (from-to)946-958
Number of pages13
JournalChem
Volume1
Issue number6
Early online date8 Dec 2016
DOIs
DateAccepted/In press - 16 Nov 2016
DateE-pub ahead of print - 8 Dec 2016
DatePublished (current) - 8 Dec 2016

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.

    Research areas

  • base pairs, DNA, DNA structure, mutation, PCR, synthetic base pairs, synthetic biology, X-ray crystallography

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2451929416302364 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 582 KB, PDF-document

  • Supplementary information PDF - Figures and Tables

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2451929416302364 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 773 KB, PDF-document

  • Graphical abstract PDF

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Cell Press at http://www.sciencedirect.com/science/article/pii/S2451929416302364 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 315 KB, PDF-document

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