Metal‐Induced Point Defects in DNA: Model and Mechanisms

Abstract

The aim of this work was to study the role of H3O+ and transition-metal (TM) ions in keto-enol and amino-imino tautomeric transitions in DNA base pairs and depurination. In this regard, we discuss the thermodynamic model of ion-DNA interactions and UV display of double-proton transfer (DPT) in GC. The probabilities and energies of rare tautomeric forms of GC pairs in DNA induced by H3O+ and TMwere determined being in the range from0.02 (forMg2+) to 1 ( forCu2+), and from 0 kcal/m (for Cu2+) to 2.3 kcal/m (for Mg2+), respectively. It was shown that 3'ACC5'/5'TGG3' site of DNA double helix, which corresponds to the only triplet 5'UGG3' of RNA that codes the most valuable amino acid tryptophan, is a good target for TM ions to attack. It was also shown that the only way to obtain the tryptophan-coding 5'UGG3' triplet in RNA via transition-type G --> A point mutation caused by TM ions is their interaction with the site of a DNA double helix, which corresponds to 5'CGG3' triplet of RNA that codes arginine.

Contrasting Crystallographic Signatures of 9-Carboxypropyl Adeninium Cation: Adenine Dimerization vs Carboxylic Group Interaction

“…Of particular interest are the stability concerns where it has been shown that protonation of purine residues may lead to depurination, thus compromising the stability of nucleic acid sequences. Spontaneous DNA depurination could be considered as endogenous DNA damage that is mediated by the protonation of purine N-7 position, which is accelerated under low pH and high temperature regimes and by the presence of metal ions …”

Impact of DFT functionals on the predicted magnesium–DNA interaction: an ONIOM study

“…1). As a possible consequence of this binding, the amount of so-called rare tautomers, that is, structures arising from exchanging protons with respect to the original canonical form, might be increased [23]. Indeed, though proton transfer (PT) reactions in DNA are energetically unfavorable in the absence of external perturbations [40][41][42][43][44][45][46][47][48][49][50], metalation at N7(G) can possibly activate the transfer of the H1 proton from the N1(G) position to N3(C) leading to a rare tautomer form [51][52][53][54][55][56][57].…”

“…However, at high concentrations, metals, including Mg 2? , may play an opposite role by distorting the DNA structure or by inducing tautomeric changes in the base pairs, which might eventually yield an error in the genetic information [20][21][22][23]. It is therefore unsurprising that the influence of cations in life tissues has attracted a considerable attention and has initiated numerous experimental [24][25][26][27][28] and theoretical studies [29][30][31][32][33][34][35][36][37] aiming to unravel the biological consequences of such metal-nucleic acids interactions.…”

Influence of the Environment on the Specificity of the Mg(II) Binding to Uracil

“…Uracil is a specific base for RNA in which it pairs up with adenine. All nucleobases including uracil may exist in different tautomeric forms, and this behavior may have important biological consequences, such as point mutations 1,2 because the mispairs of DNA bases can be stabilized by metalation. 3−6 In case of RNA, the rare tautomers may be stabilized by specific tertiary interactions, and they may take part in ribozyme catalysis.…”

“…Uracil is a specific base for RNA in which it pairs up with adenine. All nucleobases including uracil may exist in different tautomeric forms, and this behavior may have important biological consequences, such as point mutations , because the mispairs of DNA bases can be stabilized by metalation. − In case of RNA, the rare tautomers may be stabilized by specific tertiary interactions, and they may take part in ribozyme catalysis. Tautomeric equilibria of the nucleobases were studied in a number of previous studies in the gas phase and in aqueous solution. − The metal ions may shift the tautomeric equilibria toward to rare enol tautomers mainly in the case of isolated adenine and thymine, while for cytosine, this event is not probable .…”