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The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C
Barbara Di Fiore1, Claudia Wurzenberger1, Norman E Davey2
1The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge CB2 1QN, UK.
Molecular Cell
|December 13, 2016
Summary
The Spindle Assembly Checkpoint (SAC) uses ABBA motifs in BubR1 to bind the Mitotic Checkpoint Complex (MCC) to the Anaphase Promoting Complex/Cyclosome (APC/C). This interaction is essential for cell cycle arrest and genomic stability.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The Spindle Assembly Checkpoint (SAC) is critical for maintaining genomic stability during cell division.
- The SAC prevents premature sister chromatid separation by inhibiting the Anaphase Promoting Complex/Cyclosome (APC/C) via the Mitotic Checkpoint Complex (MCC).
Purpose of the Study:
- To investigate the role of specific Cdc20-binding motifs in BubR1 within the MCC.
- To elucidate the mechanism by which the MCC recognizes and binds to the active APC/C-Cdc20 complex.
Main Methods:
- Site-directed mutagenesis of BubR1 to alter identified Cdc20-binding motifs.
- Biochemical assays to assess MCC binding to APC/C-Cdc20.
- Analysis of cellular responses to microtubule poisons.
Main Results:
- Mutating the two ABBA motifs in BubR1 abolished MCC binding to the APC/C.
- These mutations abrogated the SAC, leading to a failure in cell cycle arrest in response to microtubule poisons.
- The ABBA-KEN-ABBA cassette motif arrangement is highly conserved across evolution.
Conclusions:
- The ABBA motifs in BubR1 are essential for MCC recognition of active APC/C-Cdc20.
- The ABBA-KEN-ABBA cassette acts as a conserved interaction module, anchoring the MCC to the APC/C.
- This mechanism is crucial for SAC function and ensuring genomic integrity.
