Novel physico-chemical mechanism of the mutagenic tautomerisation of the Watson–Crick-like A·G and C·T DNA base mispairs: a quantum-chemical picture

Abstract

The newly discovered physico-chemical mechanism of the mutagenic tautomerisation of the long A·G and short C·T Watson–Crick DNA base mispairs was revealed for the first time. The tautomerisation of each mismatch occurs via four topologically and energetically different ways through highly stable transition states – H-bonded tight ion pairs containing protonated and deprotonated bases. These processes are accompanied by a significant rebuilding of the base mispairs with a Watson–Crick architecture into wobble mismatches, which are shifted towards both the minor and major DNA grooves and vice versa. Moreover, it was established that these tautomerisation reactions occur non-dissociatively and are accompanied by the consequent replacement of the unique patterns of the specific intermolecular interactions along the IRC. Finally, we briefly discuss the possible biological significance of the obtained results for clarifying the microstructural foundations of the origin of the spontaneous point mutations within the framework of the classical Watson–Crick tautomeric hypothesis.