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BubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signaling

dc.contributor.authorBanerjee, Ananden
dc.contributor.authorChen, Chuen
dc.contributor.authorHumphrey, Laurenen
dc.contributor.authorTyson, John J.en
dc.contributor.authorJoglekar, Ajit P.en
dc.date.accessioned2024-02-19T20:04:33Zen
dc.date.available2024-02-19T20:04:33Zen
dc.date.issued2022-06-29en
dc.description.abstractDuring mitosis, unattached kinetochores in a dividing cell activate the spindle assembly checkpoint (SAC) and delay anaphase onset by generating the anaphase-inhibitory mitotic checkpoint complex (MCC). These kinetochores generate the MCC by recruiting its constituent proteins, including BubR1. In principle, BubR1 recruitment to signaling kinetochores should increase its local concentration and promote MCC formation. However, in human cells BubR1 is mainly thought to sensitize the SAC to silencing. Whether BubR1 localization to signaling kinetochores by itself enhances SAC signaling remains unknown. Therefore, we used ectopic SAC activation (eSAC) systems to isolate two molecules that recruit BubR1 to the kinetochore, the checkpoint protein Bub1 and the KI and MELT motifs in the kinetochore protein KNL1, and observed their contribution to eSAC signaling. Our quantitative analyses and mathematical modeling show that Bub1-mediated BubR1 recruitment to the human kinetochore promotes SAC signaling and highlight BubR1’s dual role of strengthening the SAC directly and silencing it indirectly.en
dc.description.versionPublished versionen
dc.format.extent15 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN br16 (Article number)en
dc.identifier.doihttps://doi.org/10.1091/mbc.E22-03-0085en
dc.identifier.eissn1939-4586en
dc.identifier.issn1059-1524en
dc.identifier.issue10en
dc.identifier.pmid35767360en
dc.identifier.urihttps://hdl.handle.net/10919/118049en
dc.identifier.volume33en
dc.language.isoenen
dc.publisherAmerican Society for Cell Biologyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35767360en
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en
dc.subjectKnl1en
dc.subjectPhosphorylationen
dc.subjectBindingen
dc.subjectLocalizationen
dc.subjectComplexesen
dc.subjectCohesionen
dc.subjectRevealsen
dc.subjectKinaseen
dc.subjectSwitchen
dc.subjectPlk1en
dc.subject.meshKinetochoresen
dc.subject.meshHumansen
dc.subject.meshCell Cycle Proteinsen
dc.subject.meshSignal Transductionen
dc.subject.meshMitosisen
dc.subject.meshCell Cycle Checkpointsen
dc.subject.meshM Phase Cell Cycle Checkpointsen
dc.subject.meshSpindle Apparatusen
dc.subject.meshProtein Serine-Threonine Kinasesen
dc.titleBubR1 recruitment to the kinetochore via Bub1 enhances spindle assembly checkpoint signalingen
dc.title.serialMolecular Biology of The Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Dean of Scienceen

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