The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1
Agnes Grallert1, Yvonne Connolly, Duncan L Smith
1CRUK Cell Division Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK.
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 conserved. 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.
Insights
The fission yeast Sid2-Mob1 kinase, part of the septum initiation network (SIN), regulates mitotic commitment in G2 phase. It activates Fin1 kinase, a transient event crucial for cell cycle timing.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mitotic exit involves reversing phosphorylation and cell division (cytokinesis).
- The Septum Initiation Network (SIN) in fission yeast controls cytokinesis, unlike the broader Mitotic Exit Network (MEN) in budding yeast.
- Core SIN-MEN components are thought to function only at mitosis's end.
Purpose of the Study:
- To investigate potential roles of SIN components beyond mitosis.
- To explore the function of the NDR kinase Sid2-Mob1 in the cell cycle.
- To understand the regulation of mitotic commitment timing.
Main Methods:
- Investigated the fission yeast Septum Initiation Network (SIN).
- Focused on the NDR kinase Sid2-Mob1 and its interaction with Fin1.
- Analyzed cell cycle progression and kinase activities in G2 phase.
Main Results:
- Sid2-Mob1 functions independently of other SIN components in G2 phase.
- Sid2-Mob1 promotes mitotic commitment by activating the NIMA-related kinase Fin1.
- Fin1 activation is transient, modulating the Pom1/Cdr1/Cdr2 network's activity towards Wee1.
Conclusions:
- Fission yeast Sid2-Mob1 has a novel role in regulating mitotic commitment timing during G2 phase.
- The study reveals a new function for a core SIN component, extending its known role.
- Fin1 kinase activation by Sid2-Mob1 represents a transient G2 event critical for cell cycle progression.
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