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.
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24 December 2001
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December 24 2001
Polyploids require Bik1 for kinetochore–microtubule attachment
Haijiang Lin,
Haijiang Lin
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
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Pedro de Carvalho,
Pedro de Carvalho
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
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David Kho,
David Kho
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
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Chin-Yin Tai,
Chin-Yin Tai
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
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Philippe Pierre,
Philippe Pierre
2Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France
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Gerald R. Fink,
Gerald R. Fink
3Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142
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David Pellman
David Pellman
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
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Haijiang Lin
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
Pedro de Carvalho
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
David Kho
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
Chin-Yin Tai
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
Philippe Pierre
2Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France
Gerald R. Fink
3Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142
David Pellman
1Department of Pediatric Oncology and Department of Pediatric Hematology/Oncology, The Dana-Farber Cancer Institute, and The Children's Hospital, Harvard Medical School, Boston, MA 02115
Address correspondence to David Pellman, The Dana-Farber Cancer Institute, Rm M621A, 44 Binney Street, Boston, MA 02115. Tel.: (617) 632-4918. Fax: (617) 632-4864. E-mail: [email protected]
H. Lin and P. de Carvalho contributed equally to this work.
C.-Y. Tai's present address is Department of Cell Biology, University of Massachusetts Medical School, 377 Plantation Street, Worcester, MA 01605.
*
Abbreviations used in this paper: +TIP, plus end–tracking protein; Chip, chromatin immunoprecipitation; kMT, kinetochore MT; MAP, MT-associated protein; MT, microtubule.
Received:
August 22 2001
Revision Received:
November 19 2001
Accepted:
November 19 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2001
J Cell Biol (2001) 155 (7): 1173–1184.
Article history
Received:
August 22 2001
Revision Received:
November 19 2001
Accepted:
November 19 2001
Citation
Haijiang Lin, Pedro de Carvalho, David Kho, Chin-Yin Tai, Philippe Pierre, Gerald R. Fink, David Pellman; Polyploids require Bik1 for kinetochore–microtubule attachment . J Cell Biol 24 December 2001; 155 (7): 1173–1184. doi: https://doi.org/10.1083/jcb.200108119
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