The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C
Publication Date
2016-12-15Journal Title
Molecular Cell
ISSN
1097-2765
Publisher
Elsevier
Volume
64
Issue
6
Pages
1144-1153
Language
English
Type
Article
This Version
VoR
Metadata
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Di Fiore, B., Wurzenberger, C., Davey, N., & Pines, J. (2016). The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C. Molecular Cell, 64 (6), 1144-1153. https://doi.org/10.1016/j.molcel.2016.11.006
Abstract
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons. These ABBA motifs flank a KEN box to form a cassette that is highly conserved through evolution, both in the arrangement and spacing of the ABBA-KEN-ABBA motifs, and association with the amino-terminal KEN box required to form the MCC. We propose that the ABBA-KEN-ABBA cassette holds the MCC onto the APC/C by binding the two Cdc20 molecules in the MCC-APC/C complex.
Keywords
mitosis, checkpoint, Spindle Assembly Checkpoint, Anaphase Promoting Complex, Cyclosome, ABBA motif, BubR1, Cdc20
Sponsorship
This work was supported by an SFI Starting Investigator Research Grant (13/SIRG/2193) to N.E.D. and a CR UK Programme grant C29/A13678 to J.P. J.P. acknowledges the financial support of Wellcome Trust Grant 092096 and CR UK Grant C6946/A14492 core support to the Gurdon Institute.
Funder references
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1016/j.molcel.2016.11.006
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262048
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International