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Higher eukaryote-specific APC/C composition is a determinant of spindle assembly checkpoint importance

Thomas Wild, Magda Budzowska, Gopal Karemore, View ORCID ProfileChunaram Choudhary
doi: https://doi.org/10.1101/222422
Thomas Wild
1Proteomics program, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
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Magda Budzowska
1Proteomics program, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
2Center for Chromosome Stability (CCS), Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
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Gopal Karemore
3Protein Imaging Platform, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
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Chunaram Choudhary
1Proteomics program, the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
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  • ORCID record for Chunaram Choudhary
  • For correspondence: chuna.choudhary@cpr.ku.dk
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Abstract

The multisubunit ubiquitin ligase APC/C (anaphase promoting complex/cyclosome) is essential for mitosis by promoting timely degradation of cyclin B1. Proper timing of APC/C activation is regulated by the spindle assembly checkpoint (SAC), which is initiated by the kinase MPS1 and implemented by MAD2-dependent inhibition of the APC/C. Here we analysed the contribution of the higher eukaryote-specific APC/C subunits APC7 and APC16 to APC/C composition, function and regulation. APC16 is required for APC7 assembly into the APC/C, while APC16 assembles independently of APC7. ΔAPC7 and ΔAPC16 cells display no major defects in mitotic progression, cyclin B1 degradation or SAC response. Strikingly, however, deletion of either APC7 or APC16 is sufficient to provide synthetic viability to MAD2 deletion. ΔAPC7ΔMAD2 cells display an accelerated mitosis and require SAC-independent MPS1 function for maintaining their genome stability. Overall, these results show how human APC/C composition critically influences the cellular fate upon loss of SAC activity.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 20, 2017.
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Higher eukaryote-specific APC/C composition is a determinant of spindle assembly checkpoint importance
Thomas Wild, Magda Budzowska, Gopal Karemore, Chunaram Choudhary
bioRxiv 222422; doi: https://doi.org/10.1101/222422
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Higher eukaryote-specific APC/C composition is a determinant of spindle assembly checkpoint importance
Thomas Wild, Magda Budzowska, Gopal Karemore, Chunaram Choudhary
bioRxiv 222422; doi: https://doi.org/10.1101/222422

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