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

doi:10.1016/j.chempr.2016.11.009

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

^*Corresponding author for this work

School of Biochemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	946-958
Number of pages	13
Journal	Chem
Volume	1
Issue number	6
Early online date	8 Dec 2016
DOIs	https://doi.org/10.1016/j.chempr.2016.11.009
Publication status	Published - 8 Dec 2016

Keywords

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

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Accepted author manuscript, 316 KB

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title = "Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System",

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.",

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

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AU - Reichenbach, Linus F.

AU - Sobri, Ahmad Ahmad

AU - Zaccai, Nathan R.

AU - Agnew, Christopher

AU - Burton, Nicholas

AU - Eperon, Lucy P.

AU - de Ornellas, Sara

AU - Eperon, Ian C.

AU - Brady, R. Leo

AU - Burley, Glenn A.

PY - 2016/12/8

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N2 - 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.

AB - 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.

KW - base pairs

KW - DNA

KW - DNA structure

KW - mutation

KW - PCR

KW - synthetic base pairs

KW - synthetic biology

KW - X-ray crystallography

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U2 - 10.1016/j.chempr.2016.11.009

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SN - 2451-9308

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EP - 958

JO - Chem

JF - Chem

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ER -

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

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A synthetic biology approach to fighting Francisella tularensis: Development of aptamer presenting DNA-nanorings

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

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