Dynamic basis for dG•dT misincorporation via tautomerization and ionization.

ABSTRACT: Tautomeric and anionic Watson-Crick-like mismatches have important roles in replication and translation errors through mechanisms that are not fully understood. Here, using NMR relaxation dispersion, we resolve a sequence-dependent kinetic network connecting G•T/U wobbles with three distinct Watson-Crick mismatches: two rapidly exchanging tautomeric species (G^enol•T/UG•T^enol/U^enol; population less than 0.4%) and one anionic species (G•T^-/U^-; population around 0.001% at neutral pH). The sequence-dependent tautomerization or ionization step was inserted into a minimal kinetic mechanism for correct incorporation during replication after the initial binding of the nucleotide, leading to accurate predictions of the probability of dG•dT misi

SUBMITTER: Kimsey IJ 

PROVIDER: S-EPMC5808992 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature