Karen Crasta, Hong Hwa Lim, Thomas H. Giddings Jr, Mark Winey and Uttam Surana*
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore.
Correspondence should be addressed to Uttam Surana: email@example.com
Published in Nature Cell Biology, 25 May 2008, Vol 10: 665-675.
Separation of duplicated centrosomes (spindle pole body or SPB in yeast) is a crucial step in the biogenesis of mitotic spindle. In vertebrate cells, centrosome separation requires the BimC family kinesin Eg5 and the activities of Cdk1 and polo kinase; however, the roles of these kinases are not fully elucidated. In budding yeast, SPB separation also requires activated Cdk1 and the plus-end kinesins Cin8 (homologous to vertebrate Eg5) and Kip1. Here we report a novel role for polo kinase in the separation of SPBs. We show that adequate accumulation of Cin8 and Kip1 requires inactivation of anaphase-promoting complex-activator Cdh1 via sequential phosphorylation by Cdk1 and polo kinase. In this process Cdk1 acts as a priming kinase in that Cdk1-mediated phosphorylation creates a binding site for polo kinase which further phosphorylates Cdh1. Thus, Cdh1 inactivation by synergistic action of Cdk1 and polo kinase provides a new paradigm for inactivation of cell cycle effectors.