Meraldi Patrick, Sorger Peter K
Department of Biology and Biological Engineering, MIT, Cambridge, MA 02139-4307, USA.
EMBO J. 2005 Apr 20;24(8):1621-33. doi: 10.1038/sj.emboj.7600641. Epub 2005 Mar 31.
The spindle checkpoint ensures faithful chromosome segregation by linking the onset of anaphase to the establishment of bipolar kinetochore-microtubule attachment. The checkpoint is mediated by a signal transduction system comprised of conserved Mad, Bub and other proteins. In this study, we use live-cell imaging coupled with RNA interference to investigate the functions of human Bub1. We find that Bub1 is essential for checkpoint control and for correct chromosome congression. Bub1 depletion leads to the accumulation of misaligned chromatids in which both sister kinetochores are linked to microtubules in an abnormal fashion, a phenotype that is unique among Mad and Bub depletions. Bub1 is similar to the Aurora B/Ipl1p kinase in having roles in both the checkpoint and microtubule binding. However, human Bub1 and Aurora B are recruited to kinetochores independently of each other and have an additive effect when depleted simultaneously. Thus, Bub1 and Aurora B appear to function in parallel pathways that promote formation of stable bipolar kinetochore-microtubule attachments.
纺锤体检查点通过将后期的开始与双极动粒-微管附着的建立联系起来，确保染色体的忠实分离。该检查点由一个由保守的Mad、Bub和其他蛋白质组成的信号转导系统介导。在本研究中，我们使用活细胞成像结合RNA干扰来研究人类Bub1的功能。我们发现Bub1对于检查点控制和正确的染色体排列至关重要。Bub1的缺失导致未对齐染色单体的积累，其中两个姐妹动粒以异常方式与微管相连，这种表型在Mad和Bub缺失中是独特的。Bub1在检查点和微管结合方面的作用与Aurora B/Ipl1p激酶相似。然而，人类Bub1和Aurora B相互独立地被招募到动粒上，并且在同时缺失时具有累加效应。因此，Bub1和Aurora B似乎在促进稳定的双极动粒-微管附着形成的平行途径中发挥作用。
