Checking fidelity in cell division Everything has to go right during cell division, so a checkpoint mechanism known as the spindle-assembly checkpoint prevents mitosis from proceeding unless the kinetochores that attach chromosomes to the spindle microtubules are properly engaged. Two papers now reveal the detailed molecular choreography that allows a single, unattached kinetochore to arrest cell division: Lara-Gonzalez et al. used a visual probe that tracks a specific form of one of the checkpoint complex proteins, and Piano et al. used a biochemical reconstitution of the checkpoint. Together, these studies reveal how protein interaction, spatial constraints, phosphorylation, and catalytic conversion of the protein Mad2 to its active form allow this all-important sensor to function. Science, this issue p. 64, p. 67 Molecular detail of the spindle-assembly checkpoint is revealed. Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive and active states of fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly of the mitotic checkpoint complex (MCC), the effector of a checkpoint required for mitotic fidelity. A catalyst assembled at kinetochores accelerates MAD2:CDC20 association through a poorly understood mechanism. Using a reconstituted SAC system, we discovered that CDC20 is an impervious substrate for which access to MAD2 requires simultaneous docking on several sites of the catalytic complex. Our analysis indicates that the checkpoint catalyst is substrate assisted and promotes MCC assembly through spatially and temporally coordinated conformational changes in both MAD2 and CDC20. This may define a paradigm for other HORMA-controlled systems.

中文翻译：

---

CDC20 协助其催化掺入有丝分裂检查点复合体

检查细胞分裂的保真度 在细胞分裂过程中，一切都必须正确进行，因此称为纺锤体组装检查点的检查点机制会阻止有丝分裂进行，除非将染色体连接到纺锤体微管的动粒正确接合。现在有两篇论文揭示了详细的分子编排，它允许单个独立的动粒阻止细胞分裂：Lara-Gonzalez 等。使用视觉探针跟踪检查点复合蛋白之一的特定形式，而 Piano 等人。使用了检查点的生化重建。总之，这些研究揭示了蛋白质相互作用、空间限制、磷酸化和蛋白质 Mad2 向其活性形式的催化转化是如何使这个非常重要的传感器发挥作用的。科学，这个问题 p。64 页。67 揭示了纺锤体组装检查点的分子细节。HORMA 结构域蛋白的开放 (O) 和封闭 (C) 拓扑分别与基本细胞通路的非活动和活动状态相关。HORMA 蛋白 O-MAD2 在与 CDC20 结合后转化为 C-MAD2。这是有丝分裂检查点复合体 (MCC) 组装的速率限制，MCC 是有丝分裂保真度所需检查点的效应器。在动粒上组装的催化剂通过一种知之甚少的机制加速了 MAD2:CDC20 的结合。使用重组的 SAC 系统，我们发现 CDC20 是一种不透水的底物，要获得 MAD2，需要同时停靠在催化复合物的几个位点上。我们的分析表明，检查点催化剂是底物辅助的，并通过 MAD2 和 CDC20 中空间和时间协调的构象变化促进 MCC 组装。这可以为其他 HORMA 控制的系统定义范例。