Currie, Cerys E., Mora-Santos, Maria, Smith, Chris, McAinsh, Andrew D. and Millar, Jonathan B. A. (2018) Bub1 is not required for the checkpoint response to unattached kinetochores in diploid human cells. Working Paper. Cold Spring Harbour: BioRXiv.

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Abstract

Error-free chromosome segregation during mitosis depends on a functional spindle assembly checkpoint (SAC). The SAC is a multi-component signaling system that is recruited to incorrectly attached kinetochores to catalyze the formation of a soluble inhibitor, known as the mitotic checkpoint complex (MCC), which binds and inhibits the anaphase promoting complex [1]. We have previously proposed that two separable pathways, composed of KNL1-Bub3-Bub1 (KBB) and Rod-Zwilch-Zw10 (RZZ), recruit Mad1-Mad2 complexes to human kinetochores to activate the SAC [2]. We refer to this as the dual pathway model. Although Bub1 is absolutely required for MCC formation in yeast (which lack RZZ), there is conflicting evidence as to whether this is also the case in human cells based on siRNA studies [2-5]. Here we report, using genome editing, that Bub1 is not strictly required for the SAC response to unattached kinetochores in human diploid hTERT-RPE1 cells, consistent with the dual pathway model.

Item Type:	Working or Discussion Paper (Working Paper)
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Journal or Publication Title:	BioRXiv
Publisher:	BioRXiv
Place of Publication:	Cold Spring Harbour
Official Date:	8 March 2018
Dates:	Date Event 8 March 2018 Published
Institution:	University of Warwick
Status:	Not Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Is Part Of:	This work was supported by MRC program grant MR/K001000/1 to A.D.M. and J.B.M. C.E.C. is funded by the BBSRC Midlands Integrative Biosciences Training Partnership (MIBTP) [grant BB/M01116X/1]. A.D.M and C.S. were also supported by a Wellcome Trust Senior Investigator Award (grant 106151/Z/14/Z) and a Royal Society Wolfson Research Merit Award (grant WM150020)

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