Kinetic approaches to understanding the mechanisms of fidelity of the herpes simplex virus type 1 DNA polymerase.
Kinetic approaches to understanding the mechanisms of fidelity of the herpes simplex virus type 1 DNA polymerase.
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DOI：
10.4061/2010/631595
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发表时间：
2010-12-13
影响因子：
2.3
通讯作者：
Parris DS
中科院分区：
文献类型：
--
作者：
Zhu Y;Stroud J;Song L;Parris DS
我们讨论了如何presteady-state和稳态动力学分析的结果的聚合和切除活动的单纯疱疹病毒1型（HSV-1）DNA聚合酶，导致更好地了解这个重要的模型复制聚合酶的保真度控制机制。尽管与其他具有内在3′至5′核酸外切酶（exo）活性的复制型聚合酶相比，错误掺入频率较差，但HSV-1 DNA复制保真度通过延伸含有错配或无碱基损伤的引物/模板的高动力学屏障以及聚合酶在exo和聚合活性位点之间切换引物末端的动态能力而增强。具有催化失活的外切活性的HSV-1聚合酶具有降低的引物转换速率，并且不能支持生产性复制，这表明靶向聚合酶用于复制抑制的新方法。
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.