Role of CDK in replication initiation
Role of CDK in replication initiation
复制标题
CDK 在复制启动中的作用
DOI：
10.1007/978-3-319-24696-3_13
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Tanaka;S. and Araki;H.
细胞周期蛋白依赖性激酶（CDKs）是真核生物细胞周期进程的主要调节因子。合成期（S期）的开始是染色体DNA复制的起始，是一个主要的细胞周期事件，也受CDK的调节。染色体DNA复制在真核生物中以两步反应发生。在第一个反应中，称为复制许可或解旋酶加载，复制解旋酶（Mcm 2 -7复合物）以无活性形式加载到复制起点上。在第二个反应中，称为起始反应或解旋酶活化，复制性解旋酶被活化，双链DNA解旋以起始DNA合成。活性复制解旋酶复合物由Cdc 45、Mcm 2 -7复合物和GINS复合物组成，称为CMG（Cdc 45-Mcm 2 -7-GINS）复合物。在起始反应中，许多复制蛋白组装到Mcm 2 -7复合物上以促进CMG复合物的形成，并且该反应由两种蛋白激酶触发，S期特异性CDK（S-CDK）和Dbf 4依赖性激酶（DDK）。每个激酶负责酵母中起始反应的不同步骤：首先，Cdc 45以DDK依赖性方式加载到许可的来源上。随后，GINS以S-CDK依赖性方式加载到原点上。CMG复合物的组分和激酶的需求在模式真核生物中是高度保守的。因此，引发反应的总体原理似乎在真核生物中高度保守，尽管反应所需的其他复制蛋白似乎不太保守，并且在CDK控制下的一组因子在物种之间可能略有不同。在本章中，我们重点讨论了S-CDK在引发反应中的作用。
Cyclin-dependent kinases (CDKs) are master regulators of cell-cycle progression in eukaryotes. The onset of the synthesis phase (S phase), which is the initiation of chromosomal DNA replication, is a major cell-cycle event that is also regulated by CDKs. Chromosomal DNA replication occurs as a two-step reaction in eukaryotes. In the first reaction, which is termed replication licensing or helicase loading, replicative helicases (the Mcm2–7 complex) are loaded onto replication origins in an inactive form. In the second reaction, which is termed initiation reaction or helicase activation, replicative helicases are activated and double-stranded DNA is unwound to initiate DNA synthesis. The active replicative helicase complex consists of Cdc45, the Mcm2–7 complex, and the GINS complex, and is called the CMG (Cdc45–Mcm2–7–GINS) complex. In the initiation reaction, many replication proteins assemble onto the Mcm2–7 complex to facilitate the formation of the CMG complex, and this reaction is triggered by two protein kinases, S-phase-specific CDK (S-CDK) and Dbf4-dependent kinase (DDK). Each kinase is responsible for a distinct step of the initiation reaction in yeast: first, Cdc45 is loaded onto licensed origins in a DDK-dependent manner. Subsequently, GINS is loaded onto the origins in an S-CDK-dependent manner. The components of the CMG complex and the requirements of kinases are highly conserved in model eukaryotes. Therefore, the overall rationale of the initiation reaction seems to be highly conserved in eukaryotes, although other replication proteins that are required for the reaction seem to be less conserved, and the set of factors under the control of CDK might be slightly different between species. In this chapter, we focus on the role of S-CDK in the initiation reaction.