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dc.contributor.authorMaffini, Stefano
dc.contributor.authorRainey, Michael D.
dc.contributor.authorKaczmarczyk, Agnieszka
dc.contributor.authorO'Connor, Aisling
dc.contributor.authorGaboriau, David
dc.contributor.authorMusacchio, Andrea
dc.contributor.authorSantocanale, Corrado
dc.date.accessioned2016-02-02T12:49:09Z
dc.date.available2016-02-02T12:49:09Z
dc.date.issued2016
dc.identifier.citationO'Connor A, Maffini S;Rainey MD;Kaczmarczyk A;Gaboriau D;Musacchio A;Santocanale C (2016) 'Requirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpoint'. Biology Open, 5 (1):11-19.en_IE
dc.identifier.issn2046-6390
dc.identifier.urihttp://hdl.handle.net/10379/5517
dc.description.abstractDuring mitotic arrest induced by microtubule targeting drugs, the weakening of the spindle assembly checkpoint (SAC) allows cells to progress through the cell cycle without chromosome segregation occurring. PLK1 kinase plays a major role in mitosis and emerging evidence indicates that PLK1 is also involved in establishing the checkpoint and maintaining SAC signalling. However, mechanistically, the role of PLK1 in the SAC is not fully understood, with several recent reports indicating that it can cooperate with either one of the major checkpoint kinases, Aurora B or MPS1. In this study, we assess the role of PLK1 in SAC maintenance. We find that in nocodazole-arrested U2OS cells, PLK1 activity is continuously required for maintaining Aurora B protein localisation and activity at kinetochores. Consistent with published data we find that upon PLK1 inhibition, phosphoThr3-H3, a marker of Haspin activity, is reduced. Intriguingly, Aurora B inhibition causes PLK1 to relocalise from kinetochores into fewer and much larger foci, possibly due to incomplete recruitment of outer kinetochore proteins. Importantly, PLK1 inhibition, together with partial inhibition of Aurora B, allows efficient SAC override to occur. This phenotype is more pronounced than the phenotype observed by combining the same PLK1 inhibitors with partial MPS1 inhibition. We also find that PLK1 inhibition does not obviously cooperate with Haspin inhibition to promote SAC override. These results indicate that PLK1 is directly involved in maintaining efficient SAC signalling, possibly by cooperating in a positive feedback loop with Aurora B, and that partially redundant mechanisms exist which reinforce the SAC..en_IE
dc.description.sponsorshipScience Foundation Ireland grant [08/IN.1/B2064], Science Foundation Ireland grant [12/IP/1508], Cancer-Care-West, Hardiman Research Scholarshipen_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherCompany of Biologistsen_IE
dc.relation.ispartofBiology Openen
dc.subjectPLK1 kinase activityen_IE
dc.subjectCell-Cycleen_IE
dc.subjectPLK1en_IE
dc.subjectAurora Ben_IE
dc.subjectMPS1en_IE
dc.subjectHaspinen_IE
dc.subjectSpindle assembly checkpointen_IE
dc.subjectKinase inhibitorsen_IE
dc.subjectNatural scienceen_IE
dc.titleRequirement for PLK1 kinase activity in the maintenance of a robust spindle assembly checkpointen_IE
dc.typeArticleen_IE
dc.date.updated2016-01-29T11:01:43Z
dc.identifier.doi10.1242/bio.014969
dc.local.publishedsourcehttp://bio.biologists.org/content/5/1/11en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid10534184
dc.local.contactCorrado Santocanale, School Of Natural Sciences, Nui Galway. 4115 Email: corrado.santocanale@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
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