Mad3 modulates the G₁ Cdk and acts as a timer in the Start network

Area of Science:

• Cell biology
• Molecular biology
• Genetics

Background:

• Cells must maintain size homeostasis for fitness and survival.
• Sizer, timer, and adder models describe growth and cell cycle coordination.
• Budding yeast are thought to use a sizer mechanism for cell cycle entry at Start.

Purpose of the Study:

• To elucidate the mechanistic framework controlling cell size homeostasis in budding yeast.
• To understand how proteins coordinate to achieve cell size regulation.
• To investigate the role of degradation machineries in cell cycle progression.

Main Methods:

• Investigated the roles of APC and SCF ubiquitin ligase complexes.
• Analyzed the cyclic accumulation of G1 Cyclin-dependent kinase (Cdk).
• Incorporated the centromeric-signaling protein Mad3 into the model.

Main Results:

• Intertwined APC and SCF degradation machineries drive cyclic G1 Cdk accumulation.
• Maximal G1 Cdk levels are reached at the Start of the cell cycle.
• Mad3 acts as a memory factor, linking G1 progression to the previous mitosis.
• The described mechanism exhibits timer properties.

Conclusions:

• A novel alternating-degradation device functions as a timer.
• This timer mechanism, coupled with a sizer, is crucial for cell cycle entry.
• Understanding this framework is key to cell size homeostasis in budding yeast.