Dynamics of spontaneous mutations: implications of guanine–cytosine tautomers on chromatin integrity

Abstract

This study investigates the origin and implications of spontaneous mutations within DNA, focusing on the dynamics of guanine–cytosine (GC) base pairs. We propose inter – and intramolecular hydrogen transfer as potential mechanisms for the formation of rare tautomers, which can significantly impact the structural conformity and operational integrity of chromatin. The nitrogenous bases in DNA are pivotal for genetic coding and protein synthesis, while chromatin plays a fundamental role in DNA compaction, organisation, gene expression control and genome integrity preservation. Our research identifies 56 previously unrecorded guanine–cytosine tautomers and explores diverse potential energy levels, leading to the discovery of 67 transition states across pathways. These transitions involve five distinct types of hydrogen transfer: N-H→N, N-H→O, N-H→C, C–H→N and O-H→N. Utilising an innovative approach, we establish a Markov chain to assess the probability of molecular production from the same source, unveiling insights into transitional dynamics. Furthermore, our study facilitates the identification of tautomers capable of swift conversion to the GC1 base pair, which is dependent on transition states and molecular pathways. Our findings contribute to a deeper understanding of spontaneous mutations and their impact on chromatin integrity, offering valuable insights for further research in this field.