Lin H, de Carvalho P, Kho D, Tai C Y, Pierre P, Fink G R, Pellman D
Department of Pediatric Oncology, The Dana-Farber Cancer Institute, The Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Cell Biol. 2001 Dec 24;155(7):1173-84. doi: 10.1083/jcb.200108119.
The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore-MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics.
动粒与纺锤体微管(MTs)的附着对于维持真核细胞中恒定的倍性至关重要。在此,展示了生化和成像数据,表明出芽酵母CLIP - 170的直系同源物Bik1是动粒 - MT结合界面的一个组成部分。引人注目的是,Bik1对于单倍体细胞的生存力并非必需,但在多倍体细胞中变得至关重要。对BIK1的倍性特异性需求使我们能够在不消除非同源基因的情况下对BIK1进行表征,提供了一种新方法来规避作为细胞骨架共同特征的功能重叠。在多倍体细胞中,后期之前需要Bik1来维持动粒分离,因此有助于对抗附着的姐妹染色单体弹性回缩的力。Bik1在动粒分离中的作用似乎独立于Bik1在调节MT动力学中的作用。多倍体细胞生存力需要一种参与动粒 - MT附着的蛋白质这一发现对癌症治疗具有潜在意义。