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Human chromokinesin KIF4A functions in chromosome condensation and segregation

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, onl...

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Detalles Bibliográficos
Autores principales: Mazumdar, Manjari, Sundareshan, Suma, Misteli, Tom
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172419/
https://www.ncbi.nlm.nih.gov/pubmed/15326200
http://dx.doi.org/10.1083/jcb.200401142
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author Mazumdar, Manjari
Sundareshan, Suma
Misteli, Tom
author_facet Mazumdar, Manjari
Sundareshan, Suma
Misteli, Tom
author_sort Mazumdar, Manjari
collection PubMed
description 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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spelling pubmed-21724192008-03-05 Human chromokinesin KIF4A functions in chromosome condensation and segregation Mazumdar, Manjari Sundareshan, Suma Misteli, Tom J Cell Biol Research Articles 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. The Rockefeller University Press 2004-08-30 /pmc/articles/PMC2172419/ /pubmed/15326200 http://dx.doi.org/10.1083/jcb.200401142 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Mazumdar, Manjari
Sundareshan, Suma
Misteli, Tom
Human chromokinesin KIF4A functions in chromosome condensation and segregation
title Human chromokinesin KIF4A functions in chromosome condensation and segregation
title_full Human chromokinesin KIF4A functions in chromosome condensation and segregation
title_fullStr Human chromokinesin KIF4A functions in chromosome condensation and segregation
title_full_unstemmed Human chromokinesin KIF4A functions in chromosome condensation and segregation
title_short Human chromokinesin KIF4A functions in chromosome condensation and segregation
title_sort human chromokinesin kif4a functions in chromosome condensation and segregation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172419/
https://www.ncbi.nlm.nih.gov/pubmed/15326200
http://dx.doi.org/10.1083/jcb.200401142
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