Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Biophysics, University of Michigan, Ann Arbor, MI, USA.
Department of Biophysics, University of Michigan, Ann Arbor, MI, USA.
Curr Biol. 2017 Aug 21;27(16):R816-R824. doi: 10.1016/j.cub.2017.06.012.
The eukaryotic kinetochore is a sophisticated multi-protein machine that segregates chromosomes during cell division. To ensure accurate chromosome segregation, it performs three major functions using disparate molecular mechanisms. It operates a mechanosensitive signaling cascade known as the spindle assembly checkpoint (SAC) to detect and signal the lack of attachment to spindle microtubules, and delay anaphase onset in response. In addition, after attaching to spindle microtubules, the kinetochore generates the force necessary to move chromosomes. Finally, if the two sister kinetochores on a chromosome are both attached to microtubules emanating from the same spindle pole, they activate another mechanosensitive mechanism to correct the monopolar attachments. All three of these functions maintain genome stability during cell division. The outlines of the biochemical activities responsible for these functions are now available. How the kinetochore integrates the underlying molecular mechanisms is still being elucidated. In this Review, we discuss how the nanoscale protein organization in the kinetochore, which we refer to as kinetochore 'architecture', organizes its biochemical activities to facilitate the realization and integration of emergent mechanisms underlying its three major functions. For this discussion, we will use the relatively simple budding yeast kinetochore as a model, and extrapolate insights gained from this model to elucidate functional roles of the architecture of the much more complex human kinetochore.
真核细胞的着丝粒是一种复杂的多蛋白机器，它在细胞分裂过程中分离染色体。为了确保染色体的准确分离，它使用不同的分子机制执行三大功能。它运作一个称为纺锤体组装检查点（SAC）的机械敏感信号级联反应，以检测和信号缺少与纺锤体微管的附着，并相应地延迟后期起始。此外，在附着于纺锤体微管之后，着丝粒产生移动染色体所需的力。最后，如果染色体上的两个姐妹着丝粒都附着于来自同一纺锤体极的微管上，它们会激活另一个机械敏感机制来纠正单极附着。这三个功能在细胞分裂过程中维持基因组稳定性。现在已经了解到负责这些功能的生化活性的大致轮廓。着丝粒如何整合潜在的分子机制仍在阐明中。在这篇综述中，我们讨论了着丝粒中纳米级别的蛋白质组织，即我们所谓的着丝粒“结构”，如何组织其生化活性，以促进其三大功能的潜在机制的实现和整合。为了进行讨论，我们将使用相对简单的芽殖酵母着丝粒作为模型，并从该模型中推断出结构对于更复杂的人类着丝粒的功能作用。
