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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 ?G(o) for the incorporation of a nucleotide into elongating dsDNA in solution (?G(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 ??G(o)(incorporation) = 5.2 ± 1.34 kcal mol(-1)). Importantly, these direct measurements indicate that ??G(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 ?G(o) for polymerization of correct nucleotides. These results also provide a basis for understanding how polymerases replicate DNA (or RNA) with high fidelity.

SUBMITTER: Olson AC 

PROVIDER: S-EPMC3561758 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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The energetic difference between synthesis of correct and incorrect base pairs accounts for highly accurate DNA replication.

Olson Andrew C AC   Patro Jennifer N JN   Urban Milan M   Kuchta Robert D RD  

Journal of the American Chemical Society 20130117 4


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 th  ...[more]

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