Abstract

The cell cycle is the process by which a cell duplicates its DNA during S-phase and divides its chromosomes during M-phase, creating two genetically identical daughter cells. Cell cycle events are ordered by synthesis and degradation of key cell regulators and by phosphorylation and dephosphorylation of numerous substrates. Phosphorylation can alter the activity, interactions or subcellular localization of a protein. A substrate’s phosphorylation status is the readout of competing activities of kinases and phosphatases that target each of its phosphorylation sites. In our recent study (EMBO J. 37, e98745), we performed time-resolved global phosphoproteome analysis of a period during the cell cycle known as mitotic exit. During this time, numerous cell biological events happen in fast succession but in strict order. First, at the metaphase to anaphase transition, the mitotic spindle elongates to pull maximally condensed chromosomes to opposite cell halves. Shortly after that, spindles disassemble and chromosomes decondense, before finally cell division is completed by cytokinesis. Our time-resolved phosphoproteome analysis of this period in budding yeast provided a survey of the principles of phosphoregulation used to order these events.

Highlights

  • Cyclin-dependent kinase (Cdk) is the master cell cycle regulator

  • Cdk is a proline directed serine/threonine kinase, meaning that its substrates are minimally defined by an (S/T)P motif

  • During the budding yeast cell cycle, nine different cyclins are synthesized during progression from G1 until mitosis, conferring substrate specificity through the different cell cycle stages

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Summary

Introduction

Cyclin-dependent kinase (Cdk) is the master cell cycle regulator. In complex with its regulatory cyclin subunits, Cdk phosphorylates numerous substrates at distinct cell cycle stages. A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit This allows the timely dephosphorylation of Cdk substrates during the course of mitotic exit. Phosphatases that counteract Cdk phosphorylation are essential during mitotic exit to bring about ordered substrate dephosphorylation.

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