A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• The p34(cdc2) kinase is a key regulator of the cell cycle in fission yeast.
• Dysregulation of p34(cdc2) activity can lead to cell cycle defects and death.
• Understanding novel regulators of p34(cdc2) is crucial for comprehending cell cycle control.

Purpose of the Study:

• To investigate the function of the newly identified gene srw1(+) in fission yeast.
• To determine the role of Srw1 in regulating cell cycle progression and differentiation.
• To elucidate the mechanism by which Srw1 interacts with p34(cdc2) and its associated proteins.

Main Methods:

• Isolation of srw1(+) as a multicopy suppressor of hyperactivated p34(cdc2).
• Analysis of srw1(+) deletion mutants for cell cycle defects and sterility.
• Genetic analysis involving deletion of Cig2 and inactivation of Wee1 kinase.
• Observation of Cdc13 degradation under nitrogen starvation conditions.

Main Results:

• Cells lacking srw1(+) exhibit sterility and cell cycle control defects.
• srw1(+) deletion mutants fail to arrest in G1 upon nitrogen starvation and undergo mitotic catastrophe when Wee1 kinase is partially inactivated.
• Fertility is restored in srw1(+) disruptants by deleting Cig2 or partially inactivating p34(cdc2).
• Srw1(+) shares functional similarities with rum1(+), inducing endoreplication and restoring fertility.

Conclusions:

• Srw1 controls cell differentiation and cell cycling by negatively regulating Cig2- and Cdc13-associated p34(cdc2).
• A key role of Srw1 is to down-regulate mitotic cyclin levels, particularly in nitrogen-poor environments.
• Srw1 is essential for proper cell cycle arrest and survival during nutrient starvation.