5-hydroxyuracil can form stable base pairs with all four bases in a DNA duplex

NMR studies, UV-monitored melting experiments, and ab initio calculations show that 5-hydroxyuracil, produced by the oxidative de-amination of cytosines by reactive oxygen species, can form stable base-pairs with dA, dG, dC and dT residues in a DNA duplex, providing a basis for the in-vivo incorporation of 5-hydroxyuracil during DNA replication.     

Ab initio base-pairing energies of an oxidized thymine product, 5-formyluracil, with standard DNA bases at the BSSE-free DFT and MP2 theory levels

Oxidation of the thymine methyl group produces two stable products, non-mutagenic 5-hydroxymethyluracil and highly mutagenic 5-formyluracil. We have calculated the interaction energy of base-pair formation involving 5-formyluracil bound to the natural DNA bases adenine (A), cytosine (C), guanine (G), and thymine (T), and discuss the effects of the 5-formyl group with respect to similar base-pairs containing uracil, 5-hydroxyuracil, thymine (5-methyluracil), and 5-hydroxycytosine. The interaction geometries and energies were calculated four ways: (a) using density functional theory (DFT) without basis set super-position error (BSSE) corrections, (b) using DFT with BSSE correction of geometries and energies, (c) using M?ller-Plesset second order perturbation theory (MP2) without BSSE correction, and (d) using MP2 with BSSE geometry and energy correction. All calculations used the 6-311G(d,p) basis set. Notably, we find that the A:5-formyluracil base-pair is more stable than the precursor A:T base-pair. The relative order of base-pair stabilities is A:5-Fo-U > G:5-Fo-U > C:5-Fo-U > T:5-Fo-U.     

Ab initio base-pairing energies of uracil and 5-hydroxyuracil with standard DNA bases at the BSSE-free DFT and MP2 theory levels

Oxidized cytosine product 5-hydroxyuracil has been shown to be the major chemical precursor for the GC to AT transition, the most frequent substitution mutation observed in aerobic organisms. We have calculated the interaction energy of base-pair formation involving uracil or 5-hydroxyuracil, which is formed in cells by oxidative deamination of cytosine, bound to any of the natural DNA bases, A, C, G, and T, and discuss the effects of the hydroxyl group in this respect. The base-pair geometries and energies were calculated using the 6-311G(dp) basis set under four conditions: using density functional theory (DFT) without out basis set super-position error (BSSE) correction, using DFT with BSSE correction of geometries and energies, using M?ller-Plesset second order perturbation theory (MP2) without BSSE correction, and using MP2 with BSSE geometry and energy correction. We find that the hydroxyl group of 5-HO-U (relative to U) has little effect on the base-pairs with A, C or one conformation of T, while making a substantial energy difference in base-pairs involving G or a different conformation of T. For most of the complexes studied, the BSSE-corrected energies at the DFT and MP2 levels of theory agreed to within 0.5 kcal.