Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint | Zendy

Thomas Wild | Zendy; Magda Budzowska | Zendy; Susanne Hellmuth | Zendy; Susana Eibes | Zendy; Gopal Karemore | Zendy; Marin Barišić | Zendy; Olaf Stemmann | Zendy; Chunaram Choudhary | Zendy

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Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint

Author(s) -

Thomas Wild,

Magda Budzowska,

Susanne Hellmuth,

Susana Eibes,

Gopal Karemore,

Marin Barišić,

Olaf Stemmann,

Chunaram Choudhary

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.10.104

Subject(s) - mad2 , spindle checkpoint , anaphase promoting complex , microbiology and biotechnology , mitosis , ubiquitin ligase , cyclin b1 , biology , anaphase , cyclin , cyclin b , spindle apparatus , mitotic exit , cyclin a , ubiquitin , cdc20 , chemistry , cell cycle , genetics , cell division , cyclin dependent kinase 1 , cell , gene

The multisubunit ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) is essential for mitosis by promoting timely degradation of cyclin B1. APC/C is tightly regulated by the spindle assembly checkpoint (SAC), which involves MPS1 and MAD2-dependent temporal inhibition of APC/C. We analyzed the contribution of the APC/C subunits APC7 and APC16 to APC/C composition and function in human cells. APC16 is required for APC7 assembly into APC/C, whereas APC16 assembles independently of APC7. APC7 and APC16 knockout cells display no major defects in mitotic progression, cyclin B1 degradation, or SAC response, but APC/C lacking these two subunits shows reduced ubiquitylation activity in vitro. Strikingly, deletion of APC7 or APC16 is sufficient to provide synthetic viability to MAD2 deletion. ΔAPC7ΔMAD2 cells display accelerated mitosis and require SAC-independent MPS1 function for genome stability. These findings reveal that the composition of APC/C critically influences the importance of the SAC in humans.

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