DNA polymerase enzymes make an error only once per 104−10
5 initial nucleotide insertions during DNA replication. Most currently
held models of this high fidelity cite the hydrogen bonds between complementary
pyrimidines and purines as a critical controlling factor. Testing this has
been difficult, however, since standard molecular strategies for blocking
or removing polar hydrogen-bonding groups cause changes to size and shape
as well as hydrogen bonding ability. One answer to this problem is the use
of nonpolar molecules that mimic the shape of natural DNA bases. Here we show
that a non-hydrogen-bonding shape mimic for adenine is replicated efficiently
and selectively against a nonpolar shape mimic for thymine. The results establish
that hydrogen bonds in a base pair are not absolutely required for efficient
nucleotide insertion. This adds support to the idea that shape complementarity
may play as important a role in replication as base−base hydrogen bonds.
