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The Four Causes: The Functional Architecture of Centromeres and Kinetochores
Annual Review of Genetics ( IF 11.1 ) Pub Date : 2022-09-02 , DOI: 10.1146/annurev-genet-072820-034559
Andrew D McAinsh 1, 2 , Adele L Marston 3
Affiliation  

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: ( a) What are the constituent parts, ( b) how does it assemble, ( c) what is the structure and arrangement, and ( d) 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.

中文翻译:

四个原因:着丝粒和动粒的功能结构

着丝粒是在所有真核生物有丝分裂和减数分裂过程中为染色体分离提供动力的分子机器。亚里士多德解释了我们如何认为只有当我们掌握了事物的原因时我们才了解了事物。在我们的例子中,为了了解动粒,四个原因对应于我们必须提出的问题:(a)组成部分是什么,(b)它如何组装,(c)结构和排列是什么,以及(d) 函数是什么?在这里,我们概述了当前着丝粒组装的蓝图,功能如何映射到该结构上,以及它是如何由底层着丝粒周围染色质塑造的。我们提出的着丝粒观点是可能的,因为随着体外重建、结构生物学和基因组学的最新进展,现在可以获得几乎完整的着丝粒部件列表。在许多生物体中,每个着丝粒都与多个微管结合,我们提出了一种模型来解释这种整体级结构的组织方式,借鉴了芽殖酵母中简单的一个微管-一个着丝粒设置的关键见解以及实现减数分裂染色体分离的创新。
更新日期:2022-09-02
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