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

16 Citations (Scopus)

507 Downloads (Pure)

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

Research Groups and Themes

Bristol BioDesign Institute

Keywords

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

Access to Document

10.1016/j.chempr.2016.11.009

Full-text PDF (accepted author manuscript)
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
Supplementary information PDF - Figures and Tables
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, 774 KB
Graphical abstract PDF
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, 316 KB

Handle.net

Persistent link

Cite this

@article{0f0626b4a7814f429076f04e3dfef30d,

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.",

keywords = "synthetic biology, X-ray crystallography, PCR, DNA structure, DNA, base pairs, synthetic base pairs, mutation",

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.\}",

year = "2016",

month = dec,

day = "8",

doi = "10.1016/j.chempr.2016.11.009",

language = "English",

volume = "1",

pages = "946--958",

journal = "Chem",

issn = "2451-9308",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Structural Basis of the Mispairing of an Artificially Expanded Genetic Information System

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

Y1 - 2016/12/8

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 - synthetic biology

KW - X-ray crystallography

KW - PCR

KW - DNA structure

KW - DNA

KW - base pairs

KW - synthetic base pairs

KW - mutation

UR - https://www.scopus.com/pages/publications/85006304235

U2 - 10.1016/j.chempr.2016.11.009

DO - 10.1016/j.chempr.2016.11.009

M3 - Article (Academic Journal)

AN - SCOPUS:85006304235

SN - 2451-9308

VL - 1

SP - 946

EP - 958

JO - Chem

JF - Chem

IS - 6

ER -

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

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

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

Cite this

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

Abstract

Research Groups and Themes

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

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

Cite this