Temporal and compartment-specific signals coordinate mitotic exit with spindle position

Ayse Koca Caydasi,Bahtiyar Kurtulmus,Michael Knop,Gislene Pereira,Rafael Duenas-Sanchez,Anton Khmelinskii

doi:10.1038/ncomms14129

Ayse Koca Caydasi, Bahtiyar Kurtulmus + Show 4 more

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https://doi.org/10.1038/ncomms14129

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Abstract

The spatiotemporal control of mitotic exit is crucial for faithful chromosome segregation during mitosis. In budding yeast, the mitotic exit network (MEN) drives cells out of mitosis, whereas the spindle position checkpoint (SPOC) blocks MEN activity when the anaphase spindle is mispositioned. How the SPOC operates at a molecular level remains unclear. Here, we report novel insights into how mitotic signalling pathways orchestrate chromosome segregation in time and space. We establish that the key function of the central SPOC kinase, Kin4, is to counterbalance MEN activation by the cdc fourteen early anaphase release (FEAR) network in the mother cell compartment. Remarkably, Kin4 becomes dispensable for SPOC function in the absence of FEAR. Cells lacking both FEAR and Kin4 show that FEAR contributes to mitotic exit through regulation of the SPOC component Bfa1 and the MEN kinase Cdc15. Furthermore, we uncover controls that specifically promote mitotic exit in the daughter cell compartment.

Highlights

The spatiotemporal control of mitotic exit is crucial for faithful chromosome segregation during mitosis
Faithful cell division is reliant upon the completion of two events before cells are permitted to exit mitosis: bipolar attachment of chromosomes to the mitotic spindle must occur before anaphase onset and sister chromatids must be segregated to the mother and daughter cells during anaphase
Mitotic exit is tightly linked to the two checkpoints, spindle assembly checkpoint (SAC) and spindle position checkpoint (SPOC), as their satisfaction is essential for fourteen early anaphase release (FEAR) network and mitotic exit network (MEN) activation, respectively (Fig. 1a)

Summary

Introduction

The spatiotemporal control of mitotic exit is crucial for faithful chromosome segregation during mitosis. The mitotic exit network (MEN) drives cells out of mitosis, whereas the spindle position checkpoint (SPOC) blocks MEN activity when the anaphase spindle is mispositioned. We establish that the key function of the central SPOC kinase, Kin[4], is to counterbalance MEN activation by the cdc fourteen early anaphase release (FEAR) network in the mother cell compartment. Mitotic exit is tightly linked to the two checkpoints, SAC and SPOC, as their satisfaction is essential for FEAR network and MEN activation, respectively (Fig. 1a). In this way, the cell assures equal partitioning of the genomic DNA between the progenies before exiting from mitosis. In this study we investigate how FEAR network, SPOC and polarity-associated factors communicate to assure faithful mitosis

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