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

Title data

Wild, Thomas ; Budzowska, Magda ; Hellmuth, Susanne ; Eibes, Susana ; Karemore, Gopal ; Barisic, Marin ; Stemmann, Olaf ; Choudhary, Chunaram:
Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint.
In: Cell Reports. Vol. 25 (November 2018) Issue 9 . - pp. 2317-2328.
ISSN 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2018.10.104

Abstract in another language

The multisubunit ubiquitin ligase APC/C (anapha sepromoting 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. Delta APC7DMAD2 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.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: ANAPHASE-PROMOTING COMPLEX; CHROMOSOME INSTABILITY; UBIQUITIN CHAINS; DEGRADATION; CYCLIN; MAD2; MPS1
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 26 Feb 2020 09:20
Last Modified: 26 Feb 2020 09:20
URI: https://eref.uni-bayreuth.de/id/eprint/54403