Recent theoretical work on the Watson-Crick bonded bases entering the helicase enzyme has shown that quantum effects lead to the formation of meta-stable tautomeric forms of DNA. Quantum chemical models of G-C and A-T base pairs 14 describe the potential energy surface (PES) of the double proton transfer in both canonical base pairs. The main difference between the A-T and G-C PES is that A-T has a considerable forward barrier for the tautomer formation, but a small reverse barrier that causes its tautomeric form to be highly unstable. On the other hand, G-C has a sizeable reverse barrier, giving a tautomeric lifetime that is comparable to the replication process. Moreover, quantum tunnelling leads to a fast proton exchange between the bases, 19 such that the timescale of the helicase cleavage is much slower than the proton transfer dynamics. Consequently, using a semi-classical interpretation, 14,15 the potentially mutagenic tautomeric form is continuously formed and destroyed over timescales several orders of magnitude quicker than the helicase cleavage, after which the bases are split into their monomeric forms. However, using a quantum interpretation, the tunnelling proton's wave functions evolve on a shorter timescale such that two clear probability distributions (in the canonical and tautomeric configuration) emerge. As demonstrated in previous paper, once the tautomer is formed and the DNA is opened, it is stabilised and is unlikely to revert to its canonical form due to a prohibitively large reaction barrier. Recent NMR experiments using isotopic substitution suggests that when the DNA enters the polymerase active site, the wobble tautomerisation reaction might be facilitated by tunnelling. Rangadurai et al. investigated the dynamics of the transition between a wobble and Watson-Crick-like G-T in duplex DNA by performing NMR relaxation dispersion in both H 2 O and D 2 O. The authors reported that the kinetic isotope effect (KIE) in the exchange rate between the two conformations of the mismatch was threefold slower in heavy water. This result provides the first experimental evidence supporting the hypothesis that quantum effects are involved in wobble tautomerisation.