Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States of America.
PLoS Genet. 2019 Oct 4;15(10):e1008423. doi: 10.1371/journal.pgen.1008423. eCollection 2019 Oct.
Accurate segregation of chromosomes to daughter cells is a critical aspect of cell division. It requires the kinetochores on duplicated chromosomes to biorient, attaching to microtubules from opposite poles of the cell. Bioriented attachments come under tension, while incorrect attachments lack tension and must be released to allow proper attachments to form. A well-studied error correction pathway is mediated by the Aurora B kinase, which destabilizes low tension-bearing attachments. We recently discovered that in vitro, kinetochores display an additional intrinsic tension-sensing pathway that utilizes Stu2. The contribution of kinetochore-associated Stu2 to error correction in cells, however, was unknown. Here, we identify a Stu2 mutant that abolishes its kinetochore function and show that it causes biorientation defects in vivo. We also show that this Stu2-mediated pathway functions together with the Aurora B-mediated pathway. Altogether, our work indicates that cells employ multiple pathways to ensure biorientation and the accuracy of chromosome segregation.
准确地将染色体分离到子细胞中是细胞分裂的一个关键方面。这需要复制染色体上的动粒向细胞两极的微管进行双定向附着。双定向附着会产生张力,而不正确的附着则缺乏张力,必须释放以形成正确的附着。一个研究得很好的错误修正途径是由 Aurora B 激酶介导的,它会使低张力承载的附着不稳定。我们最近发现,在体外,动粒显示出一种额外的内在张力感应途径,该途径利用了 Stu2。然而,细胞中与动粒相关的 Stu2 对错误修正的贡献尚不清楚。在这里,我们鉴定了一种突变体,它会破坏 Stu2 的动粒功能,并显示它会导致体内双定向缺陷。我们还表明,这种 Stu2 介导的途径与 Aurora B 介导的途径一起发挥作用。总的来说,我们的工作表明,细胞采用多种途径来确保双定向和染色体分离的准确性。