Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation by monitoring kinetochore attachment.
• While SAC activation is well-studied, the mechanisms of SAC disassembly remain largely unknown.
• Kinetochore protein assembly is crucial for SAC activation.

Purpose of the Study:

• To elucidate the molecular mechanisms governing the disassembly of the spindle assembly checkpoint (SAC) at kinetochores.
• To identify key proteins and pathways involved in SAC silencing after anaphase onset.

Main Methods:

• Genetic manipulation in budding yeast, including gene deletions (e.g., Bmh1, Fin1).
• Analysis of protein localization and complex formation using techniques like immunofluorescence and co-immunoprecipitation.
• Observation of chromosome segregation fidelity and cell cycle progression.

Main Results:

• Deletion of the 14-3-3 protein Bmh1 or hyperactivation of Cdc14 early anaphase release (FEAR) leads to premature SAC silencing.
• The kinetochore protein Fin1, complexed with protein phosphatase PP1, is essential for SAC disassembly.
• FEAR activation promotes Fin1-PP1 recruitment to kinetochores post-anaphase, leading to SAC protein clearance.
• Loss of Fin1 function results in persistent kinetochore association of SAC protein Bub1 after anaphase entry.

Conclusions:

• A novel mechanism for SAC disassembly involving the Fin1-PP1 complex and FEAR pathway has been identified.
• This mechanism is critical for efficient SAC silencing and ensuring chromosome segregation accuracy.
• Aberrant Fin1-kinetochore association can cause premature SAC silencing and subsequent chromosome missegregation.