Department of Biology, Stanford University, Stanford, United States.
Department of Genetics, Stanford University School of Medicine, Stanford, United States.
Elife. 2024 Aug 2;12:RP84875. doi: 10.7554/eLife.84875.
The spindle assembly checkpoint (SAC) temporally regulates mitosis by preventing progression from metaphase to anaphase until all chromosomes are correctly attached to the mitotic spindle. Centrosomes refine the spatial organization of the mitotic spindle at the spindle poles. However, centrosome loss leads to elongated mitosis, suggesting that centrosomes also inform the temporal organization of mitosis in mammalian cells. Here, we find that the mitotic delay in acentrosomal cells is enforced by the SAC in a MPS1-dependent manner, and that a SAC-dependent mitotic delay is required for bipolar cell division to occur in acentrosomal cells. Although acentrosomal cells become polyploid, polyploidy is not sufficient to cause dependency on a SAC-mediated delay to complete cell division. Rather, the division failure in absence of MPS1 activity results from mitotic exit occurring before acentrosomal spindles can become bipolar. Furthermore, prevention of centrosome separation suffices to make cell division reliant on a SAC-dependent mitotic delay. Thus, centrosomes and their definition of two spindle poles early in mitosis provide a 'timely two-ness' that allows cell division to occur in absence of a SAC-dependent mitotic delay.
纺锤体组装检查点 (SAC) 通过防止从中期向后期进展来暂时调节有丝分裂，直到所有染色体都正确连接到有丝分裂纺锤体上。中心体在纺锤体两极细化有丝分裂纺锤体的空间组织。然而，中心体的丢失会导致有丝分裂延长，这表明中心体也告知哺乳动物细胞有丝分裂的时间组织。在这里，我们发现无中心体细胞中的有丝分裂延迟是通过 MPS1 依赖性的 SAC 强制执行的，并且 SAC 依赖性的有丝分裂延迟对于无中心体细胞中两极细胞分裂的发生是必需的。尽管无中心体的细胞成为多倍体，但多倍体不足以导致对 SAC 介导的延迟来完成细胞分裂的依赖性。相反，在无 MPS1 活性的情况下，有丝分裂的退出发生在无中心体纺锤体能够成为两极之前，导致分裂失败。此外，防止中心体分离足以使细胞分裂依赖于 SAC 依赖性的有丝分裂延迟。因此，早期有丝分裂中中心体及其定义的两个纺锤体极提供了一种“及时的两重性”，允许在没有 SAC 依赖性有丝分裂延迟的情况下发生细胞分裂。
