Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F

被引:97
作者
Bomont, P
Maddox, P
Shah, JV
Desai, AB
Cleveland, DW
机构
[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA
关键词
centromere associated protein CENP-F; kinetochore; Mad1; Mad2; microtubule;
D O I
10.1038/sj.emboj.7600848
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
to become an abundant nuclear protein in G2, assembles at kinetochores in late G2, remains kinetochore-bound until anaphase, and is degraded at the end of mitosis. Here we show that the absence of nuclear CENP-F does not affect cell cycle progression in S and G2. In a subset of CENP-F depleted cells, kinetochore assembly fails completely, thereby provoking massive chromosome mis-segregation. In contrast, the majority of CENP-F depleted cells exhibit a strong mitotic delay with reduced tension between kinetochores of aligned, bi-oriented sister chromatids and decreased stability of kinetochore microtubules. These latter kinetochores generate mitotic checkpoint signaling when unattached, recruiting maximum levels of Mad2. Use of YFP-marked Mad1 reveals that throughout the mitotic delay some aligned, CENP-F depleted kinetochores continuously recruit Mad1. Others rebind YFP-Mad1 intermittently so as to produce 'twinkling', demonstrating cycles of mitotic checkpoint reactivation and silencing and a crucial role for CENP-F in efficient assembly of a stable microtubule-kinetochore interface.
引用
收藏
页码:3927 / 3939
页数:13
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