期刊
JOURNAL OF CELL SCIENCE
卷 132, 期 12, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.231589
关键词
Chromosome segregation; Kinetochore; Microtubules; Mitosis; Spindle assembly checkpoint
类别
资金
- Oncode Institute - KWF Kankerbestrijding (Dutch Cancer Society)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) [NWO-Vici 865.12.004]
The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by monitoring kinetochore-microtubule interactions. SAC proteins are shed from kinetochores once stable attachments are achieved. Human kinetochores consist of hundreds of SAC protein recruitment modules and bind up to 20 microtubules, raising the question of how the SAC responds to intermediate attachment states. We show that one protein module ('RZZS-MAD1-MAD2') of the SAC is removed from kinetochores at low microtubule occupancy and remains absent at higher occupancies, while another module ('BUB1-BUBR1') is retained at substantial levels irrespective of attachment states. These behaviours reflect different silencing mechanisms: while BUB1 displacement is almost fully dependent on MPS1 inactivation, MAD1 (also known as MAD1L1) displacement is not. Artificially tuning the affinity of kinetochores for microtubules further shows that similar to 50% occupancy is sufficient to shed MAD2 and silence the SAC. Kinetochores thus respond as a single unit to shut down SAC signalling at submaximal occupancy states, but retain one SAC module. This may ensure continued SAC silencing on kinetochores with fluctuating occupancy states while maintaining the ability for fast SAC re-activation.
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