Accurate chromosome alignment at metaphase and subsequent segregation of condensed chromosomes is a complex process involving elaborate and only partially characterized molecular machinery. Although several spindle associated molecular motors have been shown to be essential for mitotic function, only a few chromosome arm–associated motors have been described. Here, we show that human chromokinesin human HKIF4A (HKIF4A) is an essential chromosome-associated molecular motor involved in faithful chromosome segregation. HKIF4A localizes in the nucleoplasm during interphase and on condensed chromosome arms during mitosis. It accumulates in the mid-zone from late anaphase and localizes to the cytokinetic ring during cytokinesis. RNA interference–mediated depletion of HKIF4A in human cells results in defective prometaphase organization, chromosome mis-alignment at metaphase, spindle defects, and chromosome mis-segregation. HKIF4A interacts with the condensin I and II complexes and HKIF4A depletion results in chromosome hypercondensation, suggesting that HKIF4A is required for maintaining normal chromosome architecture. Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division.
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30 August 2004
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August 23 2004
Human chromokinesin KIF4A functions in chromosome condensation and segregation
Manjari Mazumdar,
Manjari Mazumdar
1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Suma Sundareshan,
Suma Sundareshan
2Bangalore Genei Pvt. Ltd, BDA Industrial Suburb, Peenya, Bangalore 560058 India
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Tom Misteli
Tom Misteli
1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Manjari Mazumdar
1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Suma Sundareshan
2Bangalore Genei Pvt. Ltd, BDA Industrial Suburb, Peenya, Bangalore 560058 India
Tom Misteli
1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Address correspondence to Manjari Mazumdar, National Cancer Institute, National Institutes of Health, Bldg. 41, Rm. B 507, 41 Library Dr., Bethesda, MD 20892. Tel.: (301) 435-2672. Fax: (301) 496-4951. email: [email protected]
Abbreviations used in this paper: HKIF4A, human KIF4A; MT, microtubule; RNAi, RNA interference.
Received:
January 29 2004
Accepted:
July 16 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 166 (5): 613–620.
Article history
Received:
January 29 2004
Accepted:
July 16 2004
Citation
Manjari Mazumdar, Suma Sundareshan, Tom Misteli; Human chromokinesin KIF4A functions in chromosome condensation and segregation . J Cell Biol 30 August 2004; 166 (5): 613–620. doi: https://doi.org/10.1083/jcb.200401142
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