Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, United Kingdom; email:
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
Annu Rev Genet. 2022 Nov 30;56:279-314. doi: 10.1146/annurev-genet-072820-034559. Epub 2022 Sep 2.
Kinetochores are molecular machines that power chromosome segregation during the mitotic and meiotic cell divisions of all eukaryotes. Aristotle explains how we think we have knowledge of a thing only when we have grasped its cause. In our case, to gain understanding of the kinetochore, the four causes correspond to questions that we must ask: () What are the constituent parts, () how does it assemble, () what is the structure and arrangement, and () what is the function? Here we outline the current blueprint for the assembly of a kinetochore, how functions are mapped onto this architecture, and how this is shaped by the underlying pericentromeric chromatin. The view of the kinetochore that we present is possible because an almost complete parts list of the kinetochore is now available alongside recent advances using in vitro reconstitution, structural biology, and genomics. In many organisms, each kinetochore binds to multiple microtubules, and we propose a model for how this ensemble-level architecture is organized, drawing on key insights from the simple one microtubule-one kinetochore setup in budding yeast and innovations that enable meiotic chromosome segregation.
着丝粒是分子机器,在所有真核生物的有丝分裂和减数分裂细胞分裂中驱动染色体分离。亚里士多德解释说,只有当我们掌握了事物的原因时,我们才认为自己对事物有了认识。就我们而言,要了解着丝粒,这四个原因对应着我们必须要问的问题:(1)组成部分是什么,(2)它是如何组装的,(3)结构和排列如何,以及(4)功能是什么?在这里,我们概述了目前着丝粒组装的蓝图,以及功能如何映射到这个结构上,以及这种结构如何被着丝粒周围的染色质所塑造。我们提出的着丝粒观点之所以成为可能,是因为现在已经有了几乎完整的着丝粒部件清单,同时还结合了体外重组、结构生物学和基因组学的最新进展。在许多生物体中,每个着丝粒都与多个微管结合,我们提出了一个模型,解释了这个整体架构是如何组织的,该模型借鉴了芽殖酵母中单微管-单着丝粒设置的关键见解,以及使减数分裂染色体分离成为可能的创新。