Bur1 functions with TORC1 for vacuole-mediated cell cycle progression.

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The vacuole/lysosome is crucial for eukaryotic cell growth and proliferation, involving the target of rapamycin complex 1 (TORC1) pathway.
• Vacuolar function and TORC1 signaling are essential for cell division cycle progression in yeast.

Purpose of the Study:

• To investigate the role of the essential cyclin-dependent kinase Bur1 in cell cycle progression.
• To elucidate the functional relationship between Bur1 and the TORC1 pathway in yeast.

Main Methods:

• Genetic analysis of yeast mutants, including single and double mutants for BUR1 and vacuole inheritance defects.
• Assessment of cell cycle progression defects, specifically from the G1 phase.
• Sensitivity assays to rapamycin, a TORC1 inhibitor.
• In vitro phosphorylation assays to determine direct interactions between Bur1 and Sch9.

Main Results:

• A synthetic growth defect was observed in a BUR1 mutant combined with a vacuole inheritance defect.
• Both the double mutant and a bur1-267 single mutant exhibited severe defects in G1 phase cell cycle progression.
• The bur1 mutation conferred high sensitivity to rapamycin, indicating functional cooperation with TORC1.
• Bur1 directly phosphorylates Sch9, a known TORC1 target, and both are required for Sch9 activation.

Conclusions:

• The essential cyclin-dependent kinase Bur1 plays a critical role in cell cycle progression, cooperating with the TORC1 pathway.
• Bur1's function is linked to vacuolar inheritance and TORC1 signaling, impacting G1 phase progression.
• Multiple signaling inputs, including Bur1 and TORC1, converge on Sch9 to regulate cell cycle progression.