title: Kinetic approaches to understanding the mechanisms of fidelity of the herpes simplex virus type 1 DNA polymerase.
abstract: We discuss how the results of presteady-state and steady-state kinetic analysis of the polymerizing and excision activities of herpes simplex virus type 1 (HSV-1) DNA polymerase have led to a better understanding of the mechanisms controlling fidelity of this important model replication polymerase. Despite a poorer misincorporation frequency compared to other replicative polymerases with intrinsic 3' to 5' exonuclease (exo) activity, HSV-1 DNA replication fidelity is enhanced by a high kinetic barrier to extending a primer/template containing a mismatch or abasic lesion and by the dynamic ability of the polymerase to switch the primer terminus between the exo and polymerizing active sites. The HSV-1 polymerase with a catalytically inactivated exo activity possesses reduced rates of primer switching and fails to support productive replication, suggesting a novel means to target polymerase for replication inhibition.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, 2198 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jason
authors.initials: J
authors.lastname: Stroud
authors.forename: Liping
authors.initials: L
authors.lastname: Song
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Parris