Influence of DNA Structure on the Reactivity of the Guanine Radical Cation

Oxidative damage of DNA via radical cation formation is a common cause of mutagenesis, cancer and of the physiological changes associated with aging. By using state‐of‐the‐art ab initio molecular dynamics simulations, we study the mechanism that guides the first steps of this process. In the mechani...

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Bibliographic Details
Published in:Chemistry : a European journal 2004-10, Vol.10 (19), p.4846-4852
Main Authors: Gervasio, Francesco Luigi, Laio, Alessandro, Iannuzzi, Marcella, Parrinello, Michele
Format: Article
Language:English
Subjects:
charge transfer
Cytosine - metabolism
DNA
DNA - chemistry
DNA - metabolism
DNA Damage - physiology
Free Radicals - metabolism
Guanine - analogs & derivatives
Guanine - metabolism
molecular dynamics
nucleic acids
oxidation
Oxidation-Reduction
Protons
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Summary:Oxidative damage of DNA via radical cation formation is a common cause of mutagenesis, cancer and of the physiological changes associated with aging. By using state‐of‐the‐art ab initio molecular dynamics simulations, we study the mechanism that guides the first steps of this process. In the mechanism proposed here, guanine, which among the bases has the lowest oxidation potential, and the phosphate backbone play a crucial role. We found that the rate limiting step is the water protolysis. We illuminate the role of the local environment in considerably lowering the barrier. Of particular relevance in this respect is the role of the phosphate backbone. The first steps of oxidative damage in double helical DNA by the guanine radical cation are investigated. We found that the rate limiting step is the water protolysis and that the local environment plays a role in considerably lowering the barrier (1). Once the 8‐hydroxy‐7,8‐dihydroguanyl radical intermediate is formed, it is stabilized by a reprotonation of guanine N1 (2).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.200400171