ATP-Dependent Mismatch Recognition in DNA Replication Mismatch Repair

Abstract

Mismatch repair is a critical step in DNA replication that occurs after base selection and proofreading, significantly increasing fidelity. However, the mechanism of mismatch recognition has not been established for any repair enzyme. Speculations in this area mainly focus on exploiting thermodynamic equilibrium and free energy. Nevertheless, non-equilibrium processes may play a more significant role in enhancing mismatch recognition accuracy by utilizing adenosine triphosphate (ATP). This study aimed to investigate this possibility. Considering our limited knowledge of actual mismatch repair enzymes, we proposed a hypothetical enzyme that operates as a quantum system with three discrete energy levels. When the enzyme is raised to its highest energy level, a quantum transition occurs, leading to one of two low-energy levels representing potential recognition outcomes: a correct match or a mismatch. The probabilities of the two outcomes are exponentially different, determined by the energy gap between the two low energy levels. By flipping the energy gap, discrimination between mismatches and correct matches can be achieved. Within a framework that combines quantum mechanics with thermodynamics, we established a relationship between energy cost and the recognition error.