Sridhar Shreyas, Fukagawa Tatsuo
Laboratory of Chromosome Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.
Front Cell Dev Biol. 2022 Jun 20;10:862637. doi: 10.3389/fcell.2022.862637. eCollection 2022.
The assembly of a functional kinetochore on centromeric chromatin is necessary to connect chromosomes to the mitotic spindle, ensuring accurate chromosome segregation. This connecting function of the kinetochore presents multiple internal and external structural challenges. A microtubule interacting outer kinetochore and centromeric chromatin interacting inner kinetochore effectively confront forces from the external spindle and centromere, respectively. While internally, special inner kinetochore proteins, defined as "linkers," simultaneously interact with centromeric chromatin and the outer kinetochore to enable association with the mitotic spindle. With the ability to simultaneously interact with outer kinetochore components and centromeric chromatin, linker proteins such as centromere protein (CENP)-C or CENP-T in vertebrates and, additionally CENP-Q-U in yeasts, also perform the function of force propagation within the kinetochore. Recent efforts have revealed an array of linker pathways strategies to effectively recruit the largely conserved outer kinetochore. In this review, we examine these linkages used to propagate force and recruit the outer kinetochore across evolution. Further, we look at their known regulatory pathways and implications on kinetochore structural diversity and plasticity.
在着丝粒染色质上组装功能性动粒对于将染色体连接到有丝分裂纺锤体是必要的，可确保染色体精确分离。动粒的这种连接功能面临多种内部和外部结构挑战。微管相互作用的外动粒和着丝粒染色质相互作用的内动粒分别有效地对抗来自外部纺锤体和着丝粒的力。而在内部，被定义为“连接蛋白”的特殊内动粒蛋白同时与着丝粒染色质和外动粒相互作用，从而与有丝分裂纺锤体建立联系。连接蛋白如脊椎动物中的着丝粒蛋白（CENP）-C或CENP-T，以及酵母中的CENP-Q-U，由于能够同时与外动粒成分和着丝粒染色质相互作用，也在动粒内发挥力传递的功能。最近的研究揭示了一系列连接蛋白途径策略，以有效地募集高度保守的外动粒。在这篇综述中，我们研究了这些用于在进化过程中传递力和募集外动粒的连接方式。此外，我们还探讨了它们已知的调控途径以及对动粒结构多样性和可塑性的影响。
