  DNA replication fidelity is a critical issue in molecular biology.
Biochemical experiments have provided key insights on the mechanism of fidelity
control by DNAP in the past decades, whereas systematic theoretical studies on
this issue began only recently. Because of the underlying difficulties of
mathematical treatment, comprehensive surveys on the template-specific
replication kinetics are still rare. Here we proposed a first-passage approach
to address this problem, in particular the positional fidelity, for complicated
processes with high-order neighbor effects. Under biologically-relevant
conditions, we derived approximate analytical expressions of the positional
fidelity which shows intuitively how some key kinetic pathways are coordinated
to guarantee the high fidelity, as well as the high velocity, of the
replication processes. It was also shown that the fidelity at any template
position is dominantly determined by the nearest-neighbor template sequences,
which is consistent with the idea that replication mutations are randomly
distributed in the genome.
