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Cyclin B1 scaffolds MAD 1 at the kinetochore corona to activate the mitotic checkpoint
Author(s) -
Allan Lindsey A,
Camacho Reis Magda,
Ciossani Giuseppe,
Huis in ‘t Veld Pim J,
Wohlgemuth Sabine,
Kops Geert JPL,
Musacchio Andrea,
Saurin Adrian T
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103180
Subject(s) - microbiology and biotechnology , cyclin b1 , cyclin dependent kinase 1 , mitosis , cyclin , spindle checkpoint , cyclin a , g2 m dna damage checkpoint , chemistry , cyclin b , biology , cyclin d , cell cycle checkpoint , cell cycle , spindle apparatus , biochemistry , cell division , cell
Cyclin B: CDK 1 is the master kinase regulator of mitosis. We show here that, in addition to its kinase functions, mammalian Cyclin B also scaffolds a localised signalling pathway to help preserve genome stability. Cyclin B1 localises to an expanded region of the outer kinetochore, known as the corona, where it scaffolds the spindle assembly checkpoint ( SAC ) machinery by binding directly to MAD 1. In vitro reconstitutions map the key binding interface to a few acidic residues in the N‐terminal region of MAD 1, and point mutations in this sequence abolish MAD 1 corona localisation and weaken the SAC . Therefore, Cyclin B1 is the long‐sought‐after scaffold that links MAD 1 to the corona, and this specific pool of MAD 1 is needed to generate a robust SAC response. Robustness arises because Cyclin B1: MAD 1 localisation loses dependence on MPS 1 kinase after the corona has been established, ensuring that corona‐localised MAD 1 can still be phosphorylated when MPS 1 activity is low. Therefore, this study explains how corona‐ MAD 1 generates a robust SAC signal, and it reveals a scaffolding role for the key mitotic kinase, Cyclin B1: CDK 1, which ultimately helps to inhibit its own degradation.