Max Winokan

Max Winokan


Postgraduate Research Student
MPhys Physics - University of Surrey

About

My research project

My qualifications

2019
MPhys Physics
University of Surrey

Publications

Louie Slocombe, Max Winokan, Jim Al-Khalili, Marco Sacchi (2022)Proton transfer during DNA strand separation as a source of mutagenic guanine-cytosine tautomers, In: Communications chemistry5144 NATURE PORTFOLIO

Proton transfer between DNA bases can lead to mutagenic tautomers, but as their lifetimes are thought to be much shorter than DNA separation times their role during the DNA replication cycle is often overlooked. Here, the authors model the separation of the DNA base pair guanine-cytosine using density functional theory and find increased stability of the tautomer when the DNA strands unzip as they enter a helicase enzyme, effectively trapping the tautomer population. Proton transfer between the DNA bases can lead to mutagenic Guanine-Cytosine tautomers. Over the past several decades, a heated debate has emerged over the biological impact of tautomeric forms. Here, we determine that the energy required for generating tautomers radically changes during the separation of double-stranded DNA. Density Functional Theory calculations indicate that the double proton transfer in Guanine-Cytosine follows a sequential, step-like mechanism where the reaction barrier increases quasi-linearly with strand separation. These results point to increased stability of the tautomer when the DNA strands unzip as they enter the helicase, effectively trapping the tautomer population. In addition, molecular dynamics simulations indicate that the relevant strand separation time is two orders of magnitude quicker than previously thought. Our results demonstrate that the unwinding of DNA by the helicase could simultaneously slow the formation but significantly enhance the stability of tautomeric base pairs and provide a feasible pathway for spontaneous DNA mutations.