In this chapter, we formulate basic physico-chemical principles that define the microstructural nature of the origin of the spontaneous incorporation and replication point errors—transitions and transversions—arising during DNA biosynthesis. At this point, we relied on the firstly discovered ability of the DNA base mispairs to tautomerize via the sequential intrapair proton transfer and highly stable, highly polar, zwitterionic transition states, accompanied by a significant shifting of the base mispairs toward DNA minor or major grooves. These tautomeric transitions are characterized by a change in geometry—from wobble to Watson-Crick and vice versa—of the purine·pyrimidine (A·T, G·C, G·T and A·C), purine·purine (A·A, A·G and G·G) and pyrimidine·pyrimidine (С·С, С·T and Т·Т) DNA base mispairs. Reported results allow us to explain, on one side, the origin of the mutagenic tautomers at the separation of the DNA strands before replication and, on the other side, how DNA base mispairs adapt to enzymatically competent size in the tight recognition pocket of the high-fidelity DNA polymerase.
Part of the book: Mitochondrial DNA