IFOM-Firc Institute of Molecular Oncology, Milan, Italy.
EMBO J. 2009 Aug 5;28(15):2162-73. doi: 10.1038/emboj.2009.186. Epub 2009 Jul 23.
The idle assembly checkpoint acts to delay chromosome segregation until all duplicated sister chromatids are captured by the mitotic spindle. This pathway ensures that each daughter cell receives a complete copy of the genome. The high fidelity and robustness of this process have made it a subject of intense study in both the experimental and computational realms. A significant number of checkpoint proteins have been identified but how they orchestrate the communication between local spindle attachment and global cytoplasmic signalling to delay segregation is not yet understood. Here, we propose a systems view of the spindle assembly checkpoint to focus attention on the key regulators of the dynamics of this pathway. These regulators in turn have been the subject of detailed cellular measurements and computational modelling to connect molecular function to the dynamics of spindle assembly checkpoint signalling. A review of these efforts reveals the insights provided by such approaches and underscores the need for further interdisciplinary studies to reveal in full the quantitative underpinnings of this cellular control pathway.
空闲装配检查点的作用是延迟染色体分离，直到所有复制的姐妹染色单体被有丝分裂纺锤体捕获。这个途径确保每个子细胞都收到基因组的完整拷贝。这个过程的高度保真度和鲁棒性使得它成为实验和计算领域的研究热点。已经鉴定出大量的检查点蛋白，但它们如何协调局部纺锤体附着和全局细胞质信号之间的通信以延迟分离还不清楚。在这里，我们提出了一个纺锤体装配检查点的系统观点，以关注这个途径动态的关键调节剂。这些调节剂反过来又成为详细的细胞测量和计算建模的主题，以将分子功能与纺锤体装配检查点信号的动力学联系起来。对这些努力的回顾揭示了这些方法提供的见解，并强调需要进一步的跨学科研究来充分揭示这个细胞控制途径的定量基础。
