Is START a switch?

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The cell cycle in Saccharomyces cerevisiae is precisely regulated at a point called START, typically in late G1 phase.
• Progression through START is crucial for cell cycle commitment and subsequent development.
• The CLN1, CLN2, and CLN3 gene families encode cyclins essential for this transition.

Purpose of the Study:

• To elucidate the regulatory mechanisms controlling passage through START in Saccharomyces cerevisiae.
• To investigate the role of CLN cyclins and CDC28 protein kinase in START regulation.
• To understand the feedback loops and transcriptional regulation involved in cell cycle commitment.

Main Methods:

• Utilized inducible promoters to control the expression of CLN1 and CLN3.
• Analyzed cyclin-deficient yeast strains arrested in G1 phase.
• Investigated the transcriptional regulation of CLN1 and CLN2 by cell cycle-dependent regulators SWI4 and SWI6.
• Examined the role of FAR1 in inhibiting CLN function and its expression dynamics.

Main Results:

• Inducible expression of CLN1 or CLN3 enabled cyclin-deficient G1-arrested cells to traverse START.
• A model was proposed where CLN proteins activate CDC28 kinase, initiating a positive feedback loop for CLN1 and CLN2 transcription.
• SWI4 and SWI6 were identified as potential components of this feedback loop.
• Expression of FAR1, an inhibitor of CLN function, decreased at the time of START, correlating with peak CLN1 and CLN2 mRNA levels.

Conclusions:

• The interplay of CLN cyclins, CDC28 kinase, and transcriptional regulators like SWI4/SWI6 sharpens the START transition into an all-or-nothing event.
• This precise regulation ensures coordinated activation of START-dependent events for timely cell cycle progression.
• FAR1's regulated expression contributes to the abruptness of the START transition, preventing premature cell cycle commitment.