The
kinetic mechanisms by which DNA polymerases catalyze DNA replication
and repair have long been areas of active research. Recently discovered
Y-family DNA polymerases catalyze the bypass of damaged DNA bases
that would otherwise block replicative DNA polymerases and stall replication
forks. Unlike DNA polymerases from the five other families, the Y-family
DNA polymerases have flexible, solvent-accessible active sites that
are able to tolerate various types of damaged template bases and allow
for efficient lesion bypass. Their promiscuous active sites, however,
also lead to fidelities that are much lower than those observed for
other DNA polymerases and give rise to interesting mechanistic properties.
Additionally, the Y-family DNA polymerases have several other unique
structural features and undergo a set of conformational changes during
substrate binding and catalysis different from those observed for
replicative DNA polymerases. In recent years, pre-steady-state kinetic
methods have been extensively employed to reveal a wealth of information
about the catalytic properties of these fascinating noncanonical DNA
polymerases. Here, we review many of the recent findings on the kinetic
mechanisms of DNA polymerization with undamaged and damaged DNA substrates
by the Y-family DNA polymerases, and the conformational dynamics employed
by these error-prone enzymes during catalysis.