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The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1

Abstract

Mitotic exit integrates the reversal of the phosphorylation events initiated by mitotic kinases with a controlled cytokinesis event that cleaves the cell in two. The mitotic exit network (MEN) of budding yeast regulates both processes, whereas the fission yeast equivalent, the septum initiation network (SIN), controls only the execution of cytokinesis. The components and architecture of the SIN and MEN are highly conserved1. At present, it is assumed that the functions of the core SIN–MEN components are restricted to their characterized roles at the end of mitosis. We now show that the NDR (nuclear Dbf2-related) kinase component of the fission yeast SIN, Sid2–Mob1, acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. Sid2–Mob1 promotes mitotic commitment by directly activating the NIMA (Never In Mitosis)-related kinase Fin1. Fin1’s activation promotes its own destruction, thereby making Fin1 activation a transient feature of G2 phase. This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1.

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Figure 1: Fin1 kinase is destroyed twice in each cell cycle in a Cullin-, Fin1- and Sid2-dependent manner.
Figure 2: Sid2 phosphorylation of Fin1 on Ser 377, 526 and 698 promotes Fin1 activity in G2 phase before a peak of each kinase activity accompanies mitotic progression.
Figure 3: Inhibition of Sid2 or Fin1 delays mitotic commitment.
Figure 4: Sid2 and Fin1 target Cdr1/Cdr2/Pom1 to control mitotic commitment through Wee1.

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Acknowledgements

We thank T. Toda (CRUK London Research Institute, UK), S. Martin (University of Lausanne, Switzerland), P. Nurse (Crick Institute, London, UK), D. McCollum (University of Massachusetts, USA) for strains, K. Gull (Oxford University, UK) for TAT1 antibody, T. Carr (GDSC, UK) for plasmids and B. Hodgson (Paterson Insitute) for FACs analysis. This work was supported by Cancer Research UK (CRUK) grant number C147/A6058 and Swiss National Science Foundation support to V.S.

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A.G. and I.M.H. conceived the study. A.G. did all of the experimentation with the exception of the mass spectrometry. Y.C. and D.L.S. did the mass spectrometry. V.S. provided essential advice and strains for the analysis of SIN function. A.G. and I.M.H. wrote the manuscript with comments and advice from V.S.

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Correspondence to Agnes Grallert or Iain M. Hagan.

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The authors declare no competing financial interests.

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Grallert, A., Connolly, Y., Smith, D. et al. The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1. Nat Cell Biol 14, 738–745 (2012). https://doi.org/10.1038/ncb2514

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