Tetrad Graduate Program, University of California, San Francisco, CA 94143, USA; Cell & Tissue Biology Department, University of California, San Francisco, CA 94143, USA.
Tetrad Graduate Program, University of California, San Francisco, CA 94143, USA; Cell & Tissue Biology Department, University of California, San Francisco, CA 94143, USA.
Curr Opin Cell Biol. 2019 Oct;60:60-67. doi: 10.1016/j.ceb.2019.04.004. Epub 2019 May 25.
The kinetochore drives chromosome segregation at cell division. It acts as a physical link between chromosomes and dynamic microtubules, and as a signaling hub detecting and processing microtubule attachments to control anaphase onset. The mammalian kinetochore is a large macromolecular machine that forms a dynamic interface with the many microtubules that it binds. While we know most of the kinetochore's component parts, how they work together to give rise to its robust functions remains poorly understood. Here we highlight recent findings that shed light on this question, driven by an expanding physical and molecular toolkit. We present emerging principles that underlie the kinetochore's robust microtubule grip, such as redundancy, specialization, and dynamicity, and present signal processing principles that connect this microtubule grip to robust computation. Throughout, we identify open questions, and define simple engineering concepts that provide insight into kinetochore function.
着丝粒在细胞分裂时驱动染色体分离。它作为染色体和动态微管之间的物理连接,以及作为一个信号中心,检测和处理微管附着,以控制后期起始。哺乳动物着丝粒是一个大型的大分子机器,与它结合的许多微管形成一个动态界面。虽然我们知道着丝粒的大部分组成部分,但它们如何协同工作以产生其强大的功能仍然知之甚少。在这里,我们强调了最近的发现,这些发现是由不断扩展的物理和分子工具推动的。我们提出了一些基本原则,这些原则是基于着丝粒强大的微管握力,例如冗余性、专业化和动态性,并提出了将这种微管握力与强大的计算联系起来的信号处理原则。在整个过程中,我们确定了一些悬而未决的问题,并定义了一些简单的工程概念,这些概念为理解着丝粒的功能提供了思路。