dc.contributor.author	Mirkovic, Mihailo
dc.contributor.author	Hutter, Lukas H.
dc.contributor.author	Novák, Béla
dc.contributor.author	Oliveira, Raquel A.
dc.date.accessioned	2016-06-21T10:47:19Z
dc.date.available	2016-06-21T10:47:19Z
dc.date.issued	2015-10-08
dc.description.abstract	Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1) gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.	pt_PT
dc.description.sponsorship	Fundação para a Ciência e Tecnologia PhD scholarship: (SFRH/BD/52438/2013); Boehringer Ingelheim Fonds PhD fellowship program and EPSRC; Marie Curie Career Integration Grant: (MCCIG321883/CCC); EMBO Installation Grant: (IG2778); BBSRC sLoLa: (BB/MM00354X/1).	pt_PT
dc.identifier.citation	Mihailo Mirkovic, Lukas H. Hutter, Béla Novák, Raquel A. Oliveira, Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback, Cell Reports, Volume 13, Issue 3, 20 October 2015, Pages 469-478, ISSN 2211-1247, http://dx.doi.org/10.1016/j.celrep.2015.09.020. (http://www.sciencedirect.com/science/article/pii/S2211124715010311)	pt_PT
dc.identifier.doi	10.1016/j.celrep.2015.09.020	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/657
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.relation	Systems Biology of Mitosis
dc.relation.publisherversion	http://www.sciencedirect.com/science/article/pii/S2211124715010311	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/	pt_PT
dc.subject	Sister chromatid separation	pt_PT
dc.subject	Drosophila	pt_PT
dc.subject	SAC	pt_PT
dc.subject	mitosis	pt_PT
dc.title	Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardTitle	Systems Biology of Mitosis
oaire.awardURI	info:eu-repo/grantAgreement/EC/FP7/241548/EU
oaire.citation.endPage	478	pt_PT
oaire.citation.issue	3	pt_PT
oaire.citation.startPage	469	pt_PT
oaire.citation.title	Cell Reports	pt_PT
oaire.citation.volume	13	pt_PT
oaire.fundingStream	FP7
project.funder.identifier	http://doi.org/10.13039/501100008530
project.funder.name	European Commission
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	893e9741-5024-4d4e-9a1f-a02b286c5f36
relation.isProjectOfPublication.latestForDiscovery	893e9741-5024-4d4e-9a1f-a02b286c5f36

Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

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