Checkpoints couple transcription network oscillator dynamics to cell-cycle progression

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Cyclin-dependent kinases (CDKs) are proposed to control cell cycle progression in Saccharomyces cerevisiae by coupling to an oscillating transcription factor network.
• This network drives cell cycle events through distinct waves of CDK activity, but can oscillate autonomously in mutant cells.
• Mechanisms restraining this oscillator during normal cell cycle delays or arrests are unclear.

Purpose of the Study:

• To investigate the mechanisms that restrain the cell cycle oscillator during cell cycle arrest in budding yeast.
• To determine if mitotic CDK activity is sufficient to inhibit transcript oscillations in arrested cells.
• To elucidate the role of DNA replication and spindle assembly checkpoints in regulating the oscillator.

Main Methods:

• Experimental manipulation of cyclin-dependent kinase (CDK) activity in Saccharomyces cerevisiae.
• Activation of DNA replication and spindle assembly checkpoints.
• Analysis of transcript oscillations in arrested cells.
• Investigation of the role of Rad53 protein in regulating transcript oscillations.

Main Results:

• Mitotic CDK activity alone does not fully inhibit transcript oscillations in arrested cells.
• Activation of DNA replication and spindle assembly checkpoints effectively arrests the network oscillator.
• The DNA replication checkpoint effector, Rad53, partially arrests transcript oscillations.

Conclusions:

• Checkpoint mechanisms are crucial for maintaining the coupling of the cell cycle oscillator to cell cycle progression during arrest.
• Phosphorylation of network transcription factors by checkpoint proteins likely mediates this coupling.
• These findings reveal a critical regulatory role for checkpoints in preventing aberrant oscillator behavior during cell cycle arrest.