Polyploids require Bik1 for kinetochore-microtubule attachment

被引:93
作者
Lin, HJ
de Carvalho, P
Kho, D
Tai, CY
Pierre, P
Fink, GR
Pellman, D
机构
[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA
[4] CNRS Marseille Luminy, INSERM, Ctr Immunol, Marseille, France
[5] MIT, Cambridge, MA 02142 USA
[6] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
关键词
kinetechore; microtubule; ploidy; Bik1; plus end-tracking protein;
D O I
10.1083/jcb.200108119
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Bik1 is 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, Bilk1 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.
引用
收藏
页码:1173 / 1184
页数:12
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