Center for Biomedical Informatics, Harvard Medical School, Harvard University Boston, MA, USA.
Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University Oxford, UK.
Front Physiol. 2014 Sep 29;5:368. doi: 10.3389/fphys.2014.00368. eCollection 2014.
The control of chromosome segregation relies on the spindle assembly checkpoint (SAC), a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling.
染色体分离的控制依赖于纺锤体组装检查点（SAC），这是一个复杂的调控系统，通过延迟后期起始，确保高等生物中染色体分离的高保真度，直到每条染色体在有丝分裂纺锤体上正确地双定向。这一过程的核心是在狭窄的时空窗口内建立多个但特定的蛋白质-蛋白质相互作用。在这里，我们讨论了控制染色体分离的多蛋白复合物的高度动态性质，其中复杂的弱但协同相互作用网络调节信号放大，以确保适当的 SAC 反应。我们还讨论了 SAC 和动粒之间通信的当前结构理解；瞬时相互作用如何调节 SAC 的组装和拆卸，以及定义和操纵 SAC 信号传递信息流的挑战和机遇。
