Kitagawa Katsumi, Abdulle Rashid, Bansal Parmil K, Cagney Gerard, Fields Stanley, Hieter Philip
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Mol Cell. 2003 May;11(5):1201-13. doi: 10.1016/s1097-2765(03)00145-x.
The spindle checkpoint transiently prevents cell cycle progression of cells that have incurred errors or failed to complete steps during mitosis, including those involving kinetochore function. The molecular nature of the primary signal transmitted from defective kinetochores and how it is detected by the spindle checkpoint are unknown. We report biochemical evidence that Bub1, a component of the spindle checkpoint, associates with centromere (CEN) DNA via Skp1, a core kinetochore component in budding yeast. The Skp1's interaction with Bub1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization, kinetochore assembly defects, or Mps1 overexpression. We propose that the Skp1-Bub1 interaction is important for transmitting a signal to the spindle checkpoint pathway when insufficient tension is present at kinetochores.
纺锤体检查点可暂时阻止在有丝分裂期间出现错误或未能完成步骤的细胞的细胞周期进程，包括那些涉及动粒功能的细胞。从有缺陷的动粒传递的主要信号的分子本质以及纺锤体检查点如何检测该信号尚不清楚。我们报告了生化证据，表明纺锤体检查点的一个组成部分Bub1通过Skp1与着丝粒（CEN）DNA结合，Skp1是芽殖酵母中动粒的一个核心组成部分。Skp1与Bub1的相互作用是动粒张力缺陷诱导的有丝分裂延迟所必需的，但不是纺锤体解聚、动粒组装缺陷或Mps1过表达诱导的停滞所必需的。我们提出，当动粒处存在不足的张力时，Skp1-Bub1相互作用对于向纺锤体检查点途径传递信号很重要。
