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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| Format: | Article |
| Language: | English |
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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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| author | Yali Zhu Jason Stroud Liping Song Deborah S. Parris |
| author_facet | Yali Zhu Jason Stroud Liping Song Deborah S. Parris |
| author_sort | Yali Zhu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5622fe4e172544be9abde5dde31b0ce9 |
| institution | OA Journals |
| issn | 2090-021X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-5622fe4e172544be9abde5dde31b0ce92025-08-20T02:04:58ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/631595631595Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA PolymeraseYali Zhu0Jason Stroud1Liping Song2Deborah S. Parris3Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, 2198 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210, USADepartment of Molecular Genetics, The Ohio State University, 2198 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, 2198 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210, USADepartment of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, 2198 Graves Hall, 333 West Tenth Avenue, Columbus, OH 43210, USAWe 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.http://dx.doi.org/10.4061/2010/631595 |
| spellingShingle | Yali Zhu Jason Stroud Liping Song Deborah S. Parris Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase Journal of Nucleic Acids |
| title | Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase |
| title_full | Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase |
| title_fullStr | Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase |
| title_full_unstemmed | Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase |
| title_short | Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase |
| title_sort | kinetic approaches to understanding the mechanisms of fidelity of the herpes simplex virus type 1 dna polymerase |
| url | http://dx.doi.org/10.4061/2010/631595 |
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