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Electron attachment-induced DNA single-strand breaks at the pyrimidine sites

1 , 2 , * , 2 , 2 , *

Nucleic Acids Research

Oxford University Press

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      Abstract

      To elucidate the contribution of pyrimidine in DNA strand breaks caused by low-energy electrons (LEEs), theoretical investigations of the LEE attachment-induced C3′–O3′, and C5′–O5′ σ bond as well as N-glycosidic bond breaking of 2′-deoxycytidine-3′,5′-diphosphate and 2′-deoxythymidine-3′,5′-diphosphate were performed using the B3LYP/DZP++ approach. The base-centered radical anions are electronically stable enough to assure that either the C–O or glycosidic bond breaking processes might compete with the electron detachment and yield corresponding radical fragments and anions. In the gas phase, the computed glycosidic bond breaking activation energy (24.1 kcal/mol) excludes the base release pathway. The low-energy barrier for the C3′–O3′ σ bond cleavage process (∼6.0 kcal/mol for both cytidine and thymidine) suggests that this reaction pathway is the most favorable one as compared to other possible pathways. On the other hand, the relatively low activation energy barrier (∼14 kcal/mol) for the C5′–O5′ σ bond cleavage process indicates that this bond breaking pathway could be possible, especially when the incident electrons have relatively high energy (a few electronvolts). The presence of the polarizable medium greatly increases the activation energies of either C–O σ bond cleavage processes or the N-glycosidic bond breaking process. The only possible pathway that dominates the LEE-induced DNA single strands in the presence of the polarizable surroundings (such as in an aqueous solution) is the C3′–O3′ σ bond cleavage (the relatively low activation energy barrier, ∼13.4 kcal/mol, has been predicted through a polarizable continuum model investigation). The qualitative agreement between the ratio for the bond breaks of C5′–O5′, C3′–O3′ and N-glycosidic bonds observed in the experiment of oligonucleotide tetramer CGAT and the theoretical sequence of the bond breaking reaction pathways have been found. This consistency between the theoretical predictions and the experimental observations provides strong supportive evidences for the base-centered radical anion mechanism of the LEE-induced single-strand bond breaking around the pyrimidine sites of the DNA single strands.

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      Most cited references 60

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          DNA strand breaks induced by 0-4 eV electrons: the role of shape resonances.

          Collisions of 0-4 eV electrons with thin DNA films are shown to produce single strand breaks. The yield is sharply structured as a function of electron energy and indicates the involvement of pi* shape resonances in the bond breaking process. The cross sections are comparable in magnitude to those observed in other compounds in the gas phase in which pi* electrons are transferred through the molecule to break a remote bond. The results therefore support aspects of a theoretical study by Barrios et al. [J. Phys. B 106, 7991 (2002)]] indicating that such a mechanism could produce strand breaks in DNA.
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            Author and article information

            Affiliations
            1Drug Design & Discovery Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, Shanghai 201203 P. R. China and 2Interdisciplinary Nanotoxicity Center, Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS 39217, USA
            Author notes
            *To whom correspondence should be addressed. Jiande Gu. Tel: +86 21 5080 6720; Fax: +86 21 5080 7088; Email: jiandegush@ 123456go.com
            Correspondence may also be addressed to Jerzy Leszczynski. Tel: +1 601 979 3482; Fax: +1 601 979 7823; Email: jerzy@ 123456icnanotox.org
            Journal
            Nucleic Acids Res
            nar
            nar
            Nucleic Acids Research
            Oxford University Press
            0305-1048
            1362-4962
            September 2010
            September 2010
            29 April 2010
            29 April 2010
            : 38
            : 16
            : 5280-5290
            2938206
            20430827
            10.1093/nar/gkq304
            gkq304
            © The Author(s) 2010. Published by Oxford University Press.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Computational Biology

            Genetics

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