Proton transfer during DNA strand separation as a source of mutagenic guanine-cytosine tautomers.

ABSTRACT: 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

SUBMITTER: Slocombe L 

PROVIDER: S-EPMC9814255 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature