Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase.
Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase.
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DOI：
10.1016/j.celrep.2015.11.018
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发表时间：
2015-12-22
期刊：
影响因子：
8.8
通讯作者：
Lou H
中科院分区：
文献类型：
--
作者：
Quan Y;Xia Y;Liu L;Cui J;Li Z;Cao Q;Chen XS;Campbell JL;Lou H
Mcm 2 -7解旋酶在G1期作为无活性的双六聚体（DH）装载到双链起始DNA上。Mcm 2 -7重构触发S期解旋酶激活的机制尚不清楚。在这里，我们开发了一种方法来检测和纯化的内源性DHs直接。通过细胞分级分离，我们提供了体内证据表明，DH在G1期组装在染色质上，在S期分离。有趣的是，Mcm 10，一个强大的MCM相互作用，共纯化专门与DH的背景下，染色质。删除的主要相互作用域，Mcm 10 C-末端，导致生长和S相缺陷，这可以通过Mcm 10-MCM融合抑制。通过监测MCM DH的动力学，我们发现在Mcm 10-MCM相互作用缺陷突变体中，DH溶解在S期有显著延迟。因此，我们提出了一个重要的作用，Mcm 10在Mcm 2 -7重塑通过形成一个细胞周期调节的超复合物与DH。
Mcm2-7 helicase is loaded onto double stranded origin DNA as an inactive double hexamer (DH) in G1 phase. The mechanisms of Mcm2-7 remodeling to trigger helicase activation in S phase remain unknown. Here, we develop an approach to detect and purify the endogenous DHs directly. Through cellular fractionation, we provide in vivo evidence that DHs are assembled on chromatin in G1 phase and separated during S phase. Interestingly, Mcm10, a robust MCM interactor, co-purifies exclusively with the DHs in the context of chromatin. Deletion of the main interaction domain, Mcm10 C-terminus, causes growth and S phase defects, which can be suppressed through Mcm10-MCM fusions. By monitoring the dynamics of MCM DHs, we show a significant delay in DH dissolution during S phase in the Mcm10-MCM interaction deficient mutants. Therefore, we propose an essential role for Mcm10 in Mcm2-7 remodeling through formation of a cell cycle regulated supercomplex with DHs.
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影响因子：
16.6
作者：
Costa A;Hood IV;Berger JM
通讯作者：
Berger JM
DOI：
10.1073/pnas.0911500106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Evrin, Cecile;Clarke, Pippa;Speck, Christian
通讯作者：
Speck, Christian
DOI：
10.1073/pnas.94.11.5611
发表时间：
1997-05-27
影响因子：
11.1
作者：
Donovan, S;Harwood, J;Diffley, JFX
通讯作者：
Diffley, JFX
影响因子：
4.8
作者：
Robertson, Patrick D.;Warren, Eric M.;Eichman, Brandt F.
通讯作者：
Eichman, Brandt F.
影响因子：
--
作者：
Du, Wenyue;Stauffer, Melissa E;Eichman, Brandt F
通讯作者：
Eichman, Brandt F