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¹ Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
² Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605
³ School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK

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: stephen.doxsey{at}umassmed.edu

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.

Key Words: centrosome; maternal centriole; cytokinesis; cell cycle progression; MEN/SIN

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.

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