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Originally published as MBC in Press, 10.1091/mbc.E06-06-0539 on September 19, 2007

Vol. 18, Issue 12, 4847-4858, December 2007

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Distinct Sequence Elements of Cyclin B1 Promote Localization to Chromatin, Centrosomes, and Kinetochores during MitosisFormula Formula

Anna M. Bentley, Guillaume Normand, Jonathan Hoyt*, and Randall W. King

Department of Cell Biology, Harvard Medical School, Boston, MA 02115

Submitted June 20, 2006; Revised August 9, 2007; Accepted September 6, 2007
Monitoring Editor: Ted Salmon

The mitotic cyclins promote cell division by binding and activating cyclin-dependent kinases (CDKs). Each cyclin has a unique pattern of subcellular localization that plays a vital role in regulating cell division. During mitosis, cyclin B1 is known to localize to centrosomes, microtubules, and chromatin. To determine the mechanisms of cyclin B1 localization in M phase, we imaged full-length and mutant versions of human cyclin B1-enhanced green fluorescent protein in live cells by using spinning disk confocal microscopy. In addition to centrosome, microtubule, and chromatin localization, we found that cyclin B1 also localizes to unattached kinetochores after nuclear envelope breakdown. Kinetochore recruitment of cyclin B1 required the kinetochore proteins Hec1 and Mad2, and it was stimulated by microtubule destabilization. Mutagenesis studies revealed that cyclin B1 is recruited to kinetochores through both CDK1-dependent and -independent mechanisms. In contrast, localization of cyclin B1 to chromatin and centrosomes is independent of CDK1 binding. The N-terminal domain of cyclin B1 is necessary and sufficient for chromatin association, whereas centrosome recruitment relies on sequences within the cyclin box. Our data support a role for cyclin B1 function at unattached kinetochores, and they demonstrate that separable and distinct sequence elements target cyclin B1 to kinetochores, chromatin, and centrosomes during mitosis.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-06-0539) on September 19, 2007.

Formula Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

* Present address: Genome and Proteome Sciences, Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139.

Address correspondence to: Randall W. King (randy_king{at}hms.harvard.edu).

Abbreviations used: APC/C, anaphase-promoting complex/cyclosome; ACA, anti-centromeric antigen; CRS, cytoplasmic retention signal; D-box, Destruction box; HP, hydrophobic patch; NEB, nuclear envelope breakdown.






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