Protein phosphatase 1 in association with Bud14 inhibits mitotic exit in Saccharomyces cerevisiae.

Dilara Kocakaplan,Hüseyin Karabürk,Idil Kirdök,Seyma Nur Bektas,Cansu Dilege,Ayse Koca Caydasi

doi:10.7554/elife.72833

Abstract

Mitotic exit in budding yeast is dependent on correct orientation of the mitotic spindle along the cell polarity axis. When accurate positioning of the spindle fails, a surveillance mechanism named the spindle position checkpoint (SPOC) prevents cells from exiting mitosis. Mutants with a defective SPOC become multinucleated and lose their genomic integrity. Yet, a comprehensive understanding of the SPOC mechanism is missing. In this study, we identified the type 1 protein phosphatase, Glc7, in association with its regulatory protein Bud14 as a novel checkpoint component. We further showed that Glc7-Bud14 promotes dephosphorylation of the SPOC effector protein Bfa1. Our results suggest a model in which two mechanisms act in parallel for a robust checkpoint response: first, the SPOC kinase Kin4 isolates Bfa1 away from the inhibitory kinase Cdc5, and second, Glc7-Bud14 dephosphorylates Bfa1 to fully activate the checkpoint effector.

Highlights

Budding yeast undergoes asymmetric cell division in every cell cycle and is an intrinsically polarized cell
Lte1 is a mitotic exit activator that becomes essential for mitotic exit at cold temperatures (
The exact function of Lte1 in mitotic exit is not fully understood, one of the ways that Lte1 promotes mitotic exit is by preventing binding of the Spindle Position Checkpoint (SPOC) kinase Kin4 to the SPB that has migrated into the bud and by inhibiting its activity therein (Bertazzi et al, 2011; Falk et al, 2011)

Summary

Introduction

Budding yeast undergoes asymmetric cell division in every cell cycle and is an intrinsically polarized cell. In order for the daughter cell to receive one copy of the duplicated genetic material, budding yeast has to segregate its chromosomes along its mother-to-bud polarity axis, which requires positioning of the mitotic spindle apparatus along this direction. Correct orientation of the mitotic spindle is monitored by a mitotic checkpoint named the Spindle Position Checkpoint (SPOC) in budding yeast. SPOC prevents cell cycle progression of cells that fail to orient their spindle in the mother-to-bud direction, and provides time for cells to correct their spindle orientation before mitotic exit (Adames et al, 2001; Bardin et al, 2000; Bloecher et al, 2000; Pereira et al, 2000; Yeh et al, 1995). A SPOC like checkpoint exists in Drosophila and may be present in higher eukaryotes (Cheng et al, 2008; O'Connell & Wang, 2000; Pereira & Yamashita, 2011)

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