title: Influence of DNA structure on the reactivity of the guanine radical cation.
abstract: 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.
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich, USI Campus via Giuseppe Buffi 13, 6904 Lugano, Switzerland. fgervasi@phys.chem.ethz.ch
authors.forename: Francesco Luigi
authors.initials: FL
authors.lastname: Gervasio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laio
authors.forename: Marcella
authors.initials: M
authors.lastname: Iannuzzi
authors.forename: Michele
authors.initials: M
authors.lastname: Parrinello
mesh_terms: D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D010084:Oxidation-Reduction; D011522:Protons
chemical_list: D005609:Free Radicals; D011522:Protons; D006147:Guanine; D003596:Cytosine; D004247:DNA