Centrosomes nucleate microtubules and contribute to mitotic spindle organization and function. They also participate in cytokinesis and cell cycle progression in ways that are poorly understood. Here we describe a novel human protein called centriolin that localizes to the maternal centriole and functions in both cytokinesis and cell cycle progression. Centriolin silencing induces cytokinesis failure by a novel mechanism whereby cells remain interconnected by long intercellular bridges. Most cells continue to cycle, reenter mitosis, and form multicellular syncytia. Some ultimately divide or undergo apoptosis specifically during the protracted period of cytokinesis. At later times, viable cells arrest in G1/G0. The cytokinesis activity is localized to a centriolin domain that shares homology with Nud1p and Cdc11p, budding and fission yeast proteins that anchor regulatory pathways involved in progression through the late stages of mitosis. The Nud1p-like domain of centriolin binds Bub2p, another component of the budding yeast pathway. We conclude that centriolin is required for a late stage of vertebrate cytokinesis, perhaps the final cell cleavage event, and plays a role in progression into S phase.
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12 May 2003
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May 05 2003
A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase
Adam Gromley,
Adam Gromley
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Agata Jurczyk,
Agata Jurczyk
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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James Sillibourne,
James Sillibourne
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Ensar Halilovic,
Ensar Halilovic
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Mette Mogensen,
Mette Mogensen
3School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
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Irina Groisman,
Irina Groisman
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Maureen Blomberg,
Maureen Blomberg
2Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605
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Stephen Doxsey
Stephen Doxsey
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
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Adam Gromley
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Agata Jurczyk
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
James Sillibourne
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Ensar Halilovic
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Mette Mogensen
3School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
Irina Groisman
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Maureen Blomberg
2Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605
Stephen Doxsey
1Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Address correspondence to Stephen Doxsey, University of Massachusetts Medical School, Department of Molecular Medicine, 373 Plantation Street, Suite 206, Worcester, MA 01605. Tel.: (508) 856-1613. Fax: (508) 856-4289. E-mail: [email protected]
A. Gromley and A. Jurczyk contributed equally to this work.
The online version of this article includes supplemental material.
*
Abbreviations used in this paper: MEN, mitotic exit network; RPE, retinal pigment epithelial; SIN, septation initiation network; siRNA, small interfering RNA; TACC, transforming acidic coiled-coil protein; TAD, transactivation domain.
Received:
January 27 2003
Revision Received:
March 06 2003
Accepted:
March 10 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 161 (3): 535–545.
Article history
Received:
January 27 2003
Revision Received:
March 06 2003
Accepted:
March 10 2003
Citation
Adam Gromley, Agata Jurczyk, James Sillibourne, Ensar Halilovic, Mette Mogensen, Irina Groisman, Maureen Blomberg, Stephen Doxsey; A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase . J Cell Biol 12 May 2003; 161 (3): 535–545. doi: https://doi.org/10.1083/jcb.200301105
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