Published online 2 August 2006
Nucleic Acids Research, 2006, Vol. 34, No. 13 3660-3669
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Formation of isodialuric acid lesion within DNA oligomers via one-electron oxidation of 5-hydroxyuracil: characterization, stability and excision repair
Laboratoire des Lésions des Acides Nucléiques, Département de Recherche Fondamentale sur la Matière Condensée Service de Chimie Inorganique et Biologique, UMR E3 CEA-UJF, CEA-Grenoble, F-38054 Grenoble Cedex 9, France 1 Laboratoire de Résonance Magnétique, Département de Recherche Fondamentale sur la Matière Condensée Service de Chimie Inorganique et Biologique, UMR E3 CEA-UJF, CEA-Grenoble, F-38054 Grenoble Cedex 9, France
*To whom the correspondence should be addressed. Tel: +33 4 38 78 45 58; Fax: +33 4 38 78 50 90; Email: didier.gasparutto{at}cea.fr
Received April 13, 2006. Revised June 28, 2006. Accepted June 29, 2006.
5-Hydroxyuracil is a major oxidized nucleobase that can be generated by the action of OH radical and one-electron oxidants. The latter modified base that exhibits a low ionization potential is highly susceptible to further degradation upon exposure to various oxidants. Emphasis was placed in thiswork on the formation and characterization of one-electron oxidation products of 5-hydroxyuracil within DNA fragments of defined sequence. For this purpose, 5-hydroxyuracil containing single- and double-stranded oligonucleotides of various lengths were synthesized and then exposed to the oxidizing action of iridium salts. Isodialuric acid was found to be formed almost quantitatively by a one-electron oxidation mechanism for which relevant information was inferred from a freeze-quenched ESR study. Information on the stability of isodialuric acid thus formed and its conversion products in aqueous solutions was also gained from experiments performed at acidic, neutral and alkali pHs. Moreover, biochemical features dealing with the substrate specificity of several bacterial and yeast base excision repair enzymes to remove isodialuric acid from site-specifically modified DNA fragments were determined.
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