Two central steps for initiating eukaryotic DNA replication involve loading of the Mcm2-7 helicase onto double-stranded DNA and its activation by GINS-Cdc45. To better understand these events, we determined the structures of Mcm2-7 and the CMG complex by using single-particle electron microscopy. Mcm2-7 adopts two conformations--a lock-washer-shaped spiral state and a planar, gapped-ring form--in which Mcm2 and Mcm5 flank a breach in the helicase perimeter. GINS and Cdc45 bridge this gap, forming a topologically closed assembly with a large interior channel; nucleotide binding further seals off the discontinuity between Mcm2 and Mcm5, partitioning the channel into two smaller pores. Together, our data help explain how GINS and Cdc45 activate Mcm2-7, indicate that Mcm2-7 loading may be assisted by a natural predisposition of the hexamer to form open rings, and suggest a mechanism by which the CMG complex assists DNA strand separation.

中文翻译：

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GINS 和 Cdc45 激活 MCM2-7 解旋酶的结构基础。

启动真核 DNA 复制的两个核心步骤包括将 Mcm2-7 解旋酶加载到双链 DNA 上，并通过 GINS-Cdc45 激活它。为了更好地理解这些事件，我们使用单粒子电子显微镜确定了 Mcm2-7 和 CMG 复合物的结构。Mcm2-7 采用两种构象——一个锁紧垫圈形螺旋状态和一个平面的、有间隙的环形式——其中 Mcm2 和 Mcm5 位于解旋酶周边的一个缺口的侧面。GINS 和 Cdc45 弥补了这一差距，形成了一个具有大内部通道的拓扑封闭组件；核苷酸结合进一步封闭了 Mcm2 和 Mcm5 之间的不连续性，将通道划分为两个较小的孔。总之，我们的数据有助于解释 GINS 和 Cdc45 如何激活 Mcm2-7，