| 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. |