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| Subject Categories: Cell Cycle |
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| The EMBO Journal
(2005) 24, 3927–3939, doi:10.1038/sj.emboj.7600848 Published online 27 October 2005 |
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| Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F |
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| Pascale Bomont, Paul Maddox, Jagesh V Shah1, Arshad B Desai and Don W Cleveland |
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Department of Cellular and Molecular Medicine and Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA To whom correspondence should be addressed Don W Cleveland, Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, 3080 CMM-East, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Tel.: +1 858 534 7811; Fax: +1 858 534 7659; E-mail: dcleveland@ucsd.edu 1 Present address: Department of Systems Biology, Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA Received 22 July 2005; Accepted 30 September 2005; Published online 27 October 2005. |
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| Abstract |
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| Centromere protein F (CENP-F) (or mitosin) accumulates 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. |
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| Keywords: centromere associated protein CENP-F, kinetochore, Mad1, Mad2, microtubule |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Cell Biology News and Views (01 Apr 2006) Cell division Burning the spindle at both ends Nature News and Views (22 Jan 2004) RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article The human Nup107?160 nuclear pore subcomplex contributes to proper kinetochore functions The EMBO Journal Article (04 Apr 2007) |
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