Mediator can regulate mitotic entry and direct periodic transcription in fission yeast

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Cyclin-dependent kinase 8 (Cdk8) is crucial for timely mitotic progression in fission yeast.
• Cdk8 regulation is poorly understood as it lacks T-loop phosphorylation and its partner CycC does not oscillate.
• Cdk8 is part of the conserved Mediator complex, a regulator of eukaryotic transcription linked to signaling pathways.

Purpose of the Study:

• To investigate how Mediator complex components regulate Cdk8 activity in vivo.
• To determine the role of Mediator in controlling the timing of mitotic entry.
• To elucidate the function of Mediator in cell cycle-dependent transcription.

Main Methods:

• Investigated Cdk8 activity and mitotic entry timing in fission yeast strains with deletions in Mediator components (Med12, Med13).
• Assessed phosphorylation of the Cdk8 target Fkh2.
• Examined Mediator recruitment to mitotic genes using periodic recruitment assays.
• Studied the requirement of Mediator for the transcription of mitotic genes.

Main Results:

• Deletion of Mediator components Med12 and Med13 resulted in increased Cdk8 protein levels.
• These deletions led to premature phosphorylation of Fkh2 and earlier entry into mitosis.
• Mediator was periodically recruited to clusters of mitotic genes.
• Mediator is essential for the transcription of these mitotic genes.

Conclusions:

• Mediator complex components regulate Cdk8 activity in vivo, thereby directing mitotic entry timing.
• Mediator acts as a central hub for coordinating mitotic progression and cell cycle-dependent transcription.
• Signaling pathways and activator proteins interacting with Mediator may influence cell cycle timing.