Brovarets' O. Microstructural mechanisms of the origin of the spontaneous point mutations

This thesis is devoted to the elucidation of the microstructural mechanisms of the incorporation and replication errors arising at the DNA biosynthesis. It was revealed for the first time the physico-chemical property of the base pairs with wobble and Watson-Crick geometry mutually transform into each other by the intrapair proton transfer, that is novel and principally important for understanding of the nature of the spontaneous and induced by the analogues of the nucleotide bases point mutagenesis, and allow us to understand, from the one side, in what way occurs the adaptation of the mispairs to the enzymatically competent conformation directly in the hydrophobic recognition pocket of the high-fidelity DNA-polymerase, and from the other side - the mechanism of the mutagenic tautomerisation of the Watson-Crick DNA base pairs. It was revealed for the first time that this process occurs non-dissociatively and without direct participation of the water molecules, is controlled by the highly stable transition state - tight ion pair - and is accompanied by the patterns of the specific intermolecular interactions, seqeuntially replacing each other along the intrinsic reaction coordinate. It was created internally non-contradictable and logical theory of spontaneous point mutations. It was concluded that spontaneous point mutations are evolutionary programmed in the electronic structure of the canonical DNA bases and are inevitable.