Galli Matilde, Morgan David O
Department of Physiology and Department of Biochemistry and Biophysics, University of California, 600 16(th) Street, San Francisco, CA 94143, USA.
Dev Cell. 2016 Feb 8;36(3):344-52. doi: 10.1016/j.devcel.2016.01.003.
The spindle assembly checkpoint (SAC) delays mitotic progression when chromosomes are not properly attached to microtubules of the mitotic spindle. Cells vary widely in the extent to which they delay mitotic progression upon SAC activation. To explore the mechanisms that determine checkpoint strength in different cells, we systematically measured the mitotic delay induced by microtubule disruption at different stages of embryogenesis in Caenorhabditis elegans. Strikingly, we observed a gradual increase in SAC strength after each round of division. Analysis of mutants that alter cell size or ploidy revealed that SAC strength is determined primarily by cell size and the number of kinetochores. These findings provide clear evidence in vivo that the kinetochore-to-cytoplasm ratio determines the strength of the SAC, providing new insights into why cells exhibit such large variations in their SAC responses.
纺锤体组装检查点(SAC)在染色体未正确附着于有丝分裂纺锤体的微管时,会延迟有丝分裂进程。细胞在SAC激活后延迟有丝分裂进程的程度差异很大。为了探究决定不同细胞中检查点强度的机制,我们系统地测量了秀丽隐杆线虫胚胎发育不同阶段微管破坏诱导的有丝分裂延迟。令人惊讶的是,我们观察到每一轮分裂后SAC强度都逐渐增加。对改变细胞大小或倍性的突变体的分析表明,SAC强度主要由细胞大小和动粒数量决定。这些发现为体内动粒与细胞质的比例决定SAC强度提供了明确证据,为细胞为何在SAC反应中表现出如此大的差异提供了新的见解。