Issue 5, 2008
From the journal:

Organic & Biomolecular Chemistry

Selective one-electron oxidation of duplex DNA oligomers: reaction at thymines†

Avik Ghosh,a   Abraham Joy,a   Gary B. Schuster,*a   Thierry Doukib  and  Jean Cadet*b  

* Corresponding authors

a School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA
E-mail: gary.schuster@cos.gatech.edu

b Laboratoire “Lésions des Acides Nucléiques”, SCIB-UMR E3 (CEA/UJF), Institut Nanosciences et Cryogénie, CEA/Grenoble, Grenoble cedex 9, France
E-mail: jean.cadet@cea.fr

Abstract

The one-electron oxidation of duplex DNA generates a nucleobase radical cation (electron “hole”) that migrates long distances by a hopping mechanism. The radical cation reacts irreversibly with H2O or O2 to form oxidation products (damaged bases). In normal DNA (containing the four common DNA bases), reaction occurs most frequently at guanine. However, in DNA duplexes that do not contain guanine (i.e., those comprised exclusively of A/T base pairs), we discovered that reaction occurs primarily at thymine and gives products resulting from oxidation of the T-C5 methyl group and from addition to its C5–C6 double bond. This surprising result shows that it is the relative reactivity, not the stability, of a nucleobase radical cation that determines the nature of the products formed from oxidation of DNA. A mechanism for reaction is proposed whereby a thymine radical cation may either lose a proton from its methyl group or H2O/O2 may add across its double bond. In the latter case, addition may initiate a tandem reaction that converts both thymines of a TT step to oxidation products.

Graphical abstract: Selective one-electron oxidation of duplex DNA oligomers: reaction at thymines

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Article information

DOI
https://doi.org/10.1039/B717437C
Article type
Paper
Submitted
12 Nov 2007
Accepted
03 Jan 2008
First published
30 Jan 2008

Org. Biomol. Chem., 2008,6, 916-928

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Selective one-electron oxidation of duplex DNA oligomers: reaction at thymines

A. Ghosh, A. Joy, G. B. Schuster, T. Douki and J. Cadet, Org. Biomol. Chem., 2008, 6, 916 DOI: 10.1039/B717437C

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