Kinetic Study of Transition Mutations from G–C to A–T Base Pairs in Watson–Crick DNA Base Pairs: Double Proton Transfers

Abstract

According to the Loẅdin model [Rev. Mod. Phys. 1963, 35, 724−732], the Watson−Crick guanine−cytosine (G−C) base pair is tautomerized (G*−C*) with a small probability and then replication of G*−C* produces G*−thymine (T) and adenine (A)− C* base pairs. On the basis of this model and our previous work [J. Phys. Chem. B 2020, 124, 1715−1722], we first calculated the intrinsic reaction coordinates from G*−T to G− T* using density functional theory and evaluated the probability of G*−T tautomerization to G−T* by double proton transfer (DPT) on the basis of the transition state theory. Similarly, we calculated the probability of A−C* tautomerization to A*−C by DPT. Then, according to these probabilities, we calculated the probability of transition mutations from G−C to A−T after 2 replications. The calculated probability was 1.31 × 10 −8 , a value consistent with the mutation rate previously reported by Drake et al. [Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7160−7164]. Our results suggest that DPT is one cause of the G−C → A−T transition. To investigate differences in the optical properties between G*−T and G−T* and between A−C* and A*−C, we also evaluated the infrared absorption spectra and Raman intensities for these base pairs.

Tunneling Effect in Proton Transfer: Transfer Matrix Approach

“…The black dashed line in Figure b represents the relative errors of the TP values by the TM method to the accurate TP values for the symmetric Eckart potential, and the red dashed line represents the relative errors of the TP values by the TM method to the accurate TP values for the asymmetric Eckart potential. The accurate TP value for the Eckart potential was calculated using the T Q ( E ) expressed as eq S1 in the Supporting Information in ref . Also, the relative errors were evaluated using following equation: error = | T false( E false) − T Q false( E false) T Q false( E false) | × 100 …”

“…11−18 The probability of mutation from a G-C pair to an A-T pair via a G*-T pair and an A-C* pair was also calculated. 19 Slocombe et al, for G-C → G*-C*, included environmental effects in their theory. 20 The biological significance of these tautomerizations is that they may alter the original genetic information of DNA.…”

Inter- and Intramolecular Proton Transfer in an Isolated (Cytosine–Guanine)H+ Pair: Direct Evidence from IRMPD Spectroscopy

“…Only a decade later, Löwdin proposed that a proton transfer (PT) reaction within the Watson–Crick (WC) pair could give rise to point mutations through the formation of rare tautomers . Since then, the intermolecular PT reaction between the DNA bases has received extensive experimental − and theoretical attention. − …”

Quantum Tunnelling Effects in the Guanine-Thymine Wobble Misincorporation via Tautomerism

“…While there are other sources of replication errors, the fidelity of replication primarily depends on the ability of polymerases to select and incorporate the correct complementary base (see Figure ) and reject wobble mispairs. However, it is proposed − that a wobble mismatch can form alternative tautomeric configurations that can mimic the WC geometry and lead to erroneous DNA base matches, such as wobble­(G-T) → G*-T, where G* is the tautomeric (enol) form of the G base . Watson–Crick-like mispairs have been observed in the active sites of DNA polymerases ,, and ribosomes in enzymatically competent conformations. ,, Both nuclear magnetic resonance (NMR) relaxation dispersion experiments and simulations − indicate that the concentration of tautomeric mismatches in the cellular environment is significant and has a considerable impact on the replication fidelity of the polymerase.…”