Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase
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....
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2010-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.4061/2010/631595 |
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| Summary: | 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. |
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| ISSN: | 2090-021X |