Activation of the replicative DNA helicase: breaking up is hard to do
Activation of the replicative DNA helicase: breaking up is hard to do
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DOI：
10.1016/j.ceb.2012.01.011
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发表时间：
2012-06-01
影响因子：
7.5
通讯作者：
Diffley, John F. X.
中科院分区：
文献类型：
--
作者：
Boos, Dominik;Frigola, Jordi;Diffley, John F. X.
真核基因组的精确复制是通过仔细协调复制DNA解旋酶的加载和激活来实现的，使得每个复制起点在每个细胞周期中仅解绕一次并组装功能性双向复制体。基本的微小染色体维持2 - 7（Mcm2 - 7）蛋白，包括复制DNA解旋酶的核心，首先以无活性形式装载在复制起点。然后通过将Cdc45和GINS蛋白募集到称为CMG（Cdc45，Mcm2 - 7，GINS）的全解旋酶中来激活解旋酶。这些步骤由多种机制调节，以确保Mcm2 - 7加载只能发生在G1期，而Mcm2 - 7的激活不能发生在G1期。在这里，我们回顾了最近的进展，了解这些关键反应的解旋酶加载和激活的机制为重点。
The precise duplication of the eukaryotic genome is accomplished by carefully coordinating the loading and activation of the replicative DNA helicase so that each replication origin is unwound and assembles functional bidirectional replisomes just once in each cell cycle. The essential Minichromosome Maintenance 2-7 (Mcm2-7) proteins, comprising the core of the replicative DNA helicase, are first loaded at replication origins in an inactive form. The helicase is then activated by recruitment of the Cdc45 and GINS proteins into a holo-helicase known as CMG (Cdc45, Mcm2-7, GINS). These steps are regulated by multiple mechanisms to ensure that Mcm2-7 loading can only occur during G1 phase, whilst activation of Mcm2-7 cannot occur during G1 phase. Here we review recent progress in understanding these critical reactions focusing on the mechanism of helicase loading and activation.