title: Tautomeric transition between wobble A·C DNA base mispair and Watson-Crick-like A·C* mismatch: microstructural mechanism and biological significance.
abstract: Here, we use MP2/DFT quantum-chemical methods combined with Quantum Theory of Atoms in Molecules to study the tautomeric transition between wobble A·C(w) mismatch and Watson-Crick-like A·C*(WC) base mispair, proceeding non-dissociatively via sequential proton transfer between bases through the planar, highly stable and zwitterionic TS(A∙C-)(A∙C(W)<-->A∙C&(WC)) transition state joined by the participation of (A)N6(+)H∙∙∙N4(-)(C), (A)N1(+)H∙∙∙N4(-)(C) and (A)C2(+)H∙∙∙N3(-)(C) H-bonds. Notably, the A·C(w) ↔ A·C*(WC) tautomerization reaction is accompanied by 10 unique patterns of the specific intermolecular interactions that consistently replace each other. Our data suggest that biologically significant A·C(w) → A·C*(WC) tautomerization is a kinetically controlled pathway for formation of the enzymatically competent Watson-Crick-like A·C*(WC) DNA base mispair in the essentially hydrophobic recognition pocket of the high-fidelity DNA-polymerase, responsible for the occurrence of spontaneous point AC/CA incorporation errors during DNA biosynthesis.
authors.affiliation: Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Str., 03680 Kyiv, Ukraine. dhovorun@imbg.org.ua.
authors.forename: Ol'ha O
authors.initials: OO
authors.lastname: Brovarets'
authors.forename: Dmytro M
authors.initials: DM
authors.lastname: Hovorun
mesh_terms: D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D004247:DNA; D004259:DNA-Directed DNA Polymerase