Single Strand Break in DNA Coupled to the O—P Bond Cleavage. A Computational Study

Abstract

In the present study, we consider the formation of a single strand break (SSB) in DNA via an alternative mechanism involving O-P bond splitting that was observed as a minor route to DNA damage induced by low-energy electrons (LEEs) or γ radiation. We postulate and characterize, at the B3LYP/6-31++G(**) level, a path that starts with LEE attachment to the nucleotide of thymine resulting in a stable valence radical anion localized on pyrimidine. In the next step, a proton is attached to the C5 position of thymine, producing a neutral monohydroradical of this nucleotide. This event triggers the subsequent intramolecular transfer of a sugar hydrogen atom from C3' or C5' to the C6 site of thymine. In the final elemental reaction, O-P bond dissociation takes place, which yields the phosphoryl radical and a cyclic ketone or aldehyde. Identification of the latter species as well as 5,6-dihydropyrimidines in DNA solutions irradiated with ionizing radiation could provide experimental confirmation of the suggested mechanism.

The DNA and RNA sugar–phosphate backbone emerges as the key player. An overview of quantum-chemical, structural biology and simulation studies

“…There are also theoretical studies investigating electron-attachment induced DNA strand breaks. [240][241][242][243][244][245][246][247][248] Special attention is paid especially to the effect of low-energy electrons attachment upon the DNA backbone integrity, process of C3 0 -O3 0 and C5 0 -O5 0 s-bond homolytic fission and study of concomitant metastable anions. Among other outcomes, 243 it was found that the energy barrier for C3 0 -O3 0 bond dissociation is far more lower than that of C5 0 -O5 0 and N1-C1 0 ones.…”

Protection of DNA against low-energy electrons by amino acids: a first-principles molecular dynamics study

“…Theoretical studies have mostly focused on the interaction of an excess electron with DNA components in the gas phase, beginning with isolated nucleobases [4][5][6] and extending to large systems including dinucleoside phosphate deoxyguanylyl-3 0 ,5 0 -deoxycytidine dimer [dGpdC] 2 . 7,8 In addition, the effect of the surrounding medium has been considered through microsolvation, 9,10 polarised continuum model (PCM), 11 and more recently through condensed phase simulations. 12 Experiments have been carried out on the components of DNA, on dry plasmid DNA and with thin layers of water.…”

Hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to gamma radiation and depleted uranium singly and in combination

“…DNA damage can be induced through direct or indirect actions by these stressors. Ionizing radiations may cause direct ionization of the DNA molecule and break the hydrogen bonds and/or oxygen-phosphate bonds (Razskazovskiy et al, 2000;Rak et al, 2011) thus leading to DNA strand breaks, whereas DU may affect the normal functions of DNA by binding to the DNA molecule and leading to the formation of U-DNA adduct (Stearns et al, 2005;Wilson et al, 2014). The indirect DNA damage is normally a result of oxidative damage caused by ROS (Miller et al, 2002;Miura, 2004).…”