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The review is presented of experimental and computational data on the influence of genotoxic modification of bases (deamination, alkylation, oxidation) on the structure and biological functioning of nucleic acids. Pathways are discussed for the influence of modification on coding properties of bases, on possible errors of nucleic acid biosynthesis, and on configurations of nucleotide mispairs. The atomic structure of nucleic acid fragments with modified bases and the role of base damages in mutagenesis and carcinogenesis are considered.

The possible pathways of nucleic acid synthesis errors induced by alkylation of the nitrogen bases are considered. Using the atom-atom potential method, intermolecular interaction energy is calculated for coplanar pairs containing a normal base and N- or O-methylated analogue. By analysing the calculation results in terms of the conception of recognition centers of template enzymes the base pairs, which may occur in nucleic acid biosynthesis, were found. The preferential arising of G : C leads to A : T transitions is explained by formation of m6G : T pair. m6G : A and methylated pyrimidine : pyrimidine pair formation is supposed to be the pathways of transversions. All the data available concerning DNA and RNA synthesis on templates containing methylated analogues are explained by formation of wobble-pairs, pairs with one of the nucleotides in syn-conformation and pairs with one H-bond and a short C--H ... O or C--H ... N contact.

Molecular mechanisms of base pair substitutions induced by 2-aminopurine and 2,6-diaminopurine have been proposed by calculations of nonbonded interaction energy of this substances with nucleic acid bases. The calculation results suppose that the main pathways of the transitions are wobble pair formations of these analogues with cytosine. The possibility of the transversions as a result of incorporation of 2-aminopurine and 2,6-diaminopurine in DNA have been considered. The influence of nucleotide sequences and enzymes of nucleic acid synthesis on induced mutation frequencies have been discussed.

To elucidate the role of certain atomic groups in the formation of the nucleic acid hydrate shell, we simulated the systems involving a base or a complementary pair (the base molecules are methylated in N9 of purines and in N1 of pyrimidines) and 25 water molecules using the Monte-Carlo method. All hydrophilic centers, except for N1 purines and N3 pyrimidines in complementary pairs, form hydrogen bonds (H-bonds) with water molecules. The mean numbers of H-bonds formed by different centers, and distributions of the geometric characteristics of these bonds, which appeared similar to those in crystals, have been calculated. The formation of bridges of one, two of three water molecules between hydrophilic centers was shown. The probabilities of formation of these bridges have been calculated.

Calculations of the energy of nucleic acid base interactions as a function of parameters determining mutual position of two bases in a plane have been performed. Atom-atom potential functions used include terms proportional to the first (electrostatic), sixth (or tenth for the atoms of hydrogen bond) and 12th power of interatomic distance. The calculations have shown the existence of 27 energy minima which correspond to the formation of co-planar pairs with two (or three for G : C pair) almost linear N--H...O and N--H...N hydrogen bonds. The positions of nitrogen bases bound by two hydrogen bonds in every crystal of nucleic acid components, in the complexes of polynucleotides and in tRNA are near to the positions in one of these minima. In addition for every pair there exist energy minima which correspond to the formation of one N--H...O or N--H...N and one C--H...O or C--H...N hydrogen bond. Energy behavior near minima have been investigated. The results of our calculations are in agreement with experimental data and with the calculations which employ quantum mechanical results.