Quantum Effects in DNA Replication Fidelity

One of the most important topics in molecular biology is the genetic stability of DNA. One threat to this stability comes from proton transfer reactions which lead to the formation of rare potentially mutagenic tautomers. The tautomeric bases do not follow the standard Watson-Crick base pairing rules and can potentially lead to replication errors. While the existence of the tautomeric configurations was already postulated in the original work of Watson and Crick, it is unclear if, and to what degree, the tautomers are stable and whether quantum tunnelling contributes to tautomerisation. In this work, the energy landscape of the DNA is modelled with accurate ab initio quantum chemistry methods based on density functional theory. The resulting potential energy surfaces correspond to the single and double proton transfers between the canonical and the potentially mutagenic tautomeric state. Furthermore, the DNA is treated using an open quantum systems approach based on the Wigner-Moyal Caldera-Leggett master equation with terms accounting for the dissipative and decoherent nature of the surrounding cellular environment. The combined open quantum system and chemistry modelling approach indicate that tunnelling could be relevant for a diverse range of biological scenarios in the replisome, suggesting that such proton transfer may well play a far more important role in DNA mutation than has hitherto been suggested