  Being a dual purpose enzyme, the DNA polymerase is responsible for elongation
of the newly formed DNA strand as well as cleaving the erroneous growth in case
of a misincorporation. The efficiency of replication depends on the
coordination of the polymerization and exonuclease activity of DNA polymerase.
Here we propose and analyze a minimal kinetic model of DNA replication and
determine exact expressions for the velocity of elongation and the accuracy of
replication. We first analyze the case without exonuclease activity. In that
case, accuracy is determined by a kinetic competition between stepping and
unbinding, with discrimination between correct and incorrect nucleotides in
both transitions. We then include exonuclease activity and ask how different
modes of additional discrimination in the exonuclease pathway can improve the
accuracy while limiting the detrimental effect of exonuclase on the speed of
replication. In this way, we ask how the kinetic parameters of the model have
to be set to coordinate the two activities of the enzyme for high accuracy and
high speed. The analysis also shows that the design of a replication system
does not universally have to follow the speed-accuracy trade-off rule, although
it does in the biologically realized parameter range. The accuracy of the
process is mainly controlled by the crucial role of stepping after erroneous
incorporation, which has impact on both polymerase and exonuclease activities
of DNA polymerase.
