Spatial control of the APC/C ensures the rapid degradation of cyclin B1.

Cell Cycle Chromosome Mitosis Nucleosome Ubiquitin

Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
14 Aug 2024
Historique:
received: 12 01 2024
accepted: 26 07 2024
revised: 22 07 2024
medline: 15 8 2024
pubmed: 15 8 2024
entrez: 14 8 2024
Statut: aheadofprint

Résumé

The proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is effected by the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The SAC prevents the APC/C from recognising Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle. Once chromosomes are attached, Cyclin B1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises Cyclin B1 as soon as the SAC is turned off. Here, by combining live-cell imaging, in vitro reconstitution biochemistry, and structural analysis by cryo-electron microscopy, we provide evidence that the rapid recognition of Cyclin B1 in metaphase requires spatial regulation of the APC/C. Using fluorescence cross-correlation spectroscopy, we find that Cyclin B1 and the APC/C primarily interact at the mitotic apparatus. We show that this is because Cyclin B1, like the APC/C, binds to nucleosomes, and identify an 'arginine-anchor' in the N-terminus as necessary and sufficient for binding to the nucleosome. Mutating the arginine anchor on Cyclin B1 reduces its interaction with the APC/C and delays its degradation: cells with the mutant, non-nucleosome-binding Cyclin B1 become aneuploid, demonstrating the physiological relevance of our findings. Together, our data demonstrate that mitotic chromosomes promote the efficient interaction between Cyclin B1 and the APC/C to ensure the timely degradation of Cyclin B1 and genomic stability.

Identifiants

pubmed: 39143240
doi: 10.1038/s44318-024-00194-2
pii: 10.1038/s44318-024-00194-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust (WT)
ID : 209470/Z/17/Z
Organisme : Wellcome Trust (WT)
ID : 215458/Z/19/Z
Organisme : British Society for Cell Biology (BSCB)
ID : Summer Studentship
Organisme : Cancer Research UK (CRUK)
ID : In2Research internship
Organisme : Università di Bologna (UNIBO)
ID : Internship

Informations de copyright

© 2024. The Author(s).

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Auteurs

Luca Cirillo (L)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Rose Young (R)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Sapthaswaran Veerapathiran (S)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Annalisa Roberti (A)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Molly Martin (M)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Azzah Abubacar (A)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Camilla Perosa (C)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Catherine Coates (C)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Reyhan Muhammad (R)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Theodoros I Roumeliotis (TI)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Jyoti S Choudhary (JS)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Claudio Alfieri (C)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK. claudio.alfieri@icr.ac.uk.

Jonathon Pines (J)

The Institute of Cancer Research Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK. jon.pines@icr.ac.uk.

Classifications MeSH