DNA polymerase error rate accounted for by the free-energy difference between correct and incorrect base pairs in solution

Value 0.01 unitless
Organism Generic
Reference Kunkel TA. Evolving views of DNA replication (in)fidelity. Cold Spring Harb Symp Quant Biol. 2009 74: 91-101 p.93 right columnPubMed ID19903750
Primary Source Loeb LA, Kunkel TA. Fidelity of DNA synthesis. Annu Rev Biochem. 1982 51: 429-57.PubMed ID6214209
Comments Hydrogen bonding between template bases and incoming dNTPs is clearly important for replication fidelity (In aqueous solution, these differences are 0.2–4 kcal/mol, Kunkel 2004, PMID 14988392). However, this alone is unlikely to explain high selectivity because the free-energy difference between correct and incorrect base pairs in solution accounts for error rates of ~1:100 (primary source). Thus, other ideas have been put forth to account for the higher selectivity of accurate polymerases. For example, for the incoming dNTP to hydrogen bond to a template base, water molecules that are hydrogen-bonded to the base of the incoming dNTP must be removed, thereby decreasing the entropy of the system. This magnifies the contribution of enthalpy to the free-energy difference (Petruska and Goodman 1995), thereby increasing nucleotide selectivity. Another idea supported by substantial evidence is that high nucleotide selectivity partly results from the shape complementarity in the nascent base-pair-binding pocket. The four canonical Watson–Crick base pairs are nearly identical in size and shape. Structural studies reveal that correct base pairs fit within the nascent basepair- binding pocket without steric clashes.
Entered by Uri M
ID 105468