Abstract
Duplication of centrosomes once per cell cycle is essential for bipolar spindle formation and genome maintenance and is controlled in part by cyclin-dependent kinases (Cdks). Our study identifies Sfi1, a conserved component of centrosomes, as the first Cdk substrate required to restrict centrosome duplication to once per cell cycle. We found that reducing Cdk1 phosphorylation by changing Sfi1 phosphorylation sites to nonphosphorylatable residues leads to defects in separation of duplicated spindle pole bodies (SPBs, yeast centrosomes) and to inappropriate SPB reduplication during mitosis. These cells also display defects in bipolar spindle assembly, chromosome segregation, and growth. Our findings lead to a model whereby phosphoregulation of Sfi1 by Cdk1 has the dual function of promoting SPB separation for spindle formation and preventing premature SPB duplication. In addition, we provide evidence that the protein phosphatase Cdc14 has the converse role of activating licensing, likely via dephosphorylation of Sfi1.
Highlights
Centrosomes serve as the poles of the mitotic spindle in eukaryotic cells
Cyclin-dependent kinase (Cdk), separase, and polo-like kinase 1 [2,3,4,5] are known regulators of centrosome duplication implicated in limiting this process to once per cell cycle
A decrease in Cdk1 activity levels is needed to eliminate the block to SPB duplication, allowing SPBs to become licensed, or competent, for duplication [2]
Summary
Centrosomes serve as the poles of the mitotic spindle in eukaryotic cells. Centrosome duplication only once per cell cycle is critical for bipolar spindle organization and proper chromosome segregation. Its duplication begins during the G1 phase of the cell cycle when the half-bridge, a specialized region of the nuclear envelope on one side of the SPB, elongates and a density called the satellite forms at the cytoplasmic distal tip. Sfi is positioned on the cytoplasmic side of the halfbridge in an orientation-specific manner with the N terminus proximal and the C terminus distal to the SPB [18] Based on this topology, Kilmartin and colleagues put forth a model in which Sfi is a central player in both SPB duplication and separation [18]. After completion of SPB duplication, dissociation of the Sfi C termini at the bridge from each other would allow SPB separation to occur Based on this model, it has been proposed that Sfi may serve as a
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