title: The energetic difference between synthesis of correct and incorrect base pairs accounts for highly accurate DNA replication.
abstract: To better understand the energetics of accurate DNA replication, we directly measured ΔG(o) for the incorporation of a nucleotide into elongating dsDNA in solution (ΔG(o)(incorporation)). Direct measurements of the energetic difference between synthesis of correct and incorrect base pairs found it to be much larger than previously believed (average ΔΔG(o)(incorporation) = 5.2 ± 1.34 kcal mol(-1)). Importantly, these direct measurements indicate that ΔΔG(o)(incorporation) alone can account for the energy required for highly accurate DNA replication. Evolutionarily, these results indicate that the earliest polymerases did not have to evolve sophisticated mechanisms to replicate nucleic acids; they may only have had to take advantage of the inherently more favorable ΔG(o) for polymerization of correct nucleotides. These results also provide a basis for understanding how polymerases replicate DNA (or RNA) with high fidelity.
authors: Department of Chemistry and Biochemistry, University of Colorado, UCB 215, Boulder, Colorado 80309, USA.
authors: Andrew C
authors: AC
authors: Olson
authors: Jennifer N
authors: JN
authors: Patro
authors: Milan
authors: M
authors: Urban
authors: Robert D
authors: RD
authors: Kuchta
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D004261:DNA Replication; D013816:Thermodynamics
chemical_list: D004247:DNA