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Licensing of Yeast Centrosome Duplication Requires Phosphoregulation of Sfi1
Authors:Jennifer S Avena  Shannon Burns  Zulin Yu  Christopher C Ebmeier  William M Old  Sue L Jaspersen  Mark Winey
Institution:1. Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, United States of America.; 2. Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.; 3. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.; University of California San Francisco, United States of America,
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.
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