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Originally published In Press as doi:10.1074/jbc.M705344200 on September 4, 2007

J. Biol. Chem., Vol. 282, Issue 44, 32138-32143, November 2, 2007
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The Role of Self-association in Fin1 Function on the Mitotic Spindle*

Erika L. Woodbury and David O. Morgan1

From the Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, California 94158

Stabilization of spindle microtubules during anaphase is essential for proper chromosome segregation. Fin1 is a budding yeast protein that localizes to the poles and microtubules of the spindle during anaphase and contributes to spindle stability. The N-terminal half of Fin1 is phosphorylated at multiple sites by the cyclin-dependent kinase Clb5-Cdk1, and dephosphorylation in anaphase triggers its localization to the spindle. The C-terminal half of Fin1 contains coiled-coil motifs that are required for its self-association. Here we investigated the functional importance of the two regions of Fin1. Fin1 mutants lacking the C-terminal coiled-coil domains localized to spindle pole bodies but not along spindle microtubules. These mutants failed to self-associate and displayed reduced binding to microtubules in vitro but were functional in vivo and stabilized anaphase spindles when dephosphorylated. Deletion of the Fin1 C terminus suppressed the lethal phenotypes of the phospho-mutant Fin15A. Our findings suggest that the N-terminal region of Fin1 is sufficient for its regulated function as a spindle-stabilizing factor and that this function involves association with the spindle pole body. The ability of the C-terminal region to promote Fin1 self-association and microtubule binding may underlie the lethal effects of the deregulated Fin15A mutant.


Received for publication, June 29, 2007 , and in revised form, September 4, 2007.

* This work was supported by NIGMS, the National Institutes of Health Grant GM069901. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: UCSF, Genentech Hall, Rm. N312B, 600 16th St., San Francisco, CA 94158-2517. Tel.: 415-476-6695; Fax: 415-476-5233; E-mail: David.Morgan{at}ucsf.edu.


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