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dc.contributor.authorConti, Duccio
dc.contributor.authorGul, Parveen
dc.contributor.authorIslam, Asifa
dc.contributor.authorMartín-Durán, José M
dc.contributor.authorPickersgill, Richard W
dc.contributor.authorDraviam, Viji M
dc.date.accessioned2019-12-25T05:10:03Z
dc.date.available2019-12-25T05:10:03Z
dc.date.issued2019-12-06
dc.date.submitted2019-06-14
dc.identifier.other49325
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300252
dc.descriptionFunder: Islamic Development Bank; FundRef: http://dx.doi.org/10.13039/501100003971
dc.description.abstractMicrotubules segregate chromosomes by attaching to macromolecular kinetochores. Only microtubule-end attached kinetochores can be pulled apart; how these end-on attachments are selectively recognised and stabilised is not known. Using the kinetochore and microtubule-associated protein, Astrin, as a molecular probe, we show that end-on attachments are rapidly stabilised by spatially-restricted delivery of PP1 near the C-terminus of Ndc80, a core kinetochore-microtubule linker. PP1 is delivered by the evolutionarily conserved tail of Astrin and this promotes Astrin’s own enrichment creating a highly-responsive positive feedback, independent of biorientation. Abrogating Astrin:PP1-delivery disrupts attachment stability, which is not rescued by inhibiting Aurora-B, an attachment destabiliser, but is reversed by artificially tethering PP1 near the C-terminus of Ndc80. Constitutive Astrin:PP1-delivery disrupts chromosome congression and segregation, revealing a dynamic mechanism for stabilising attachments. Thus, Astrin-PP1 mediates a dynamic ‘lock’ that selectively and rapidly stabilises end-on attachments, independent of biorientation, and ensures proper chromosome segregation.
dc.languageen
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectkinetochore
dc.subjectmicrotubule
dc.subjectmitosis
dc.subjectchromosome
dc.subjectHuman
dc.titleKinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation
dc.typeArticle
dc.date.updated2019-12-25T05:10:02Z
dc.identifier.doi10.17863/CAM.47325
dcterms.dateAccepted2019-12-01
rioxxterms.versionofrecord10.7554/elife.49325
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisorsenior_editor: Akhmanova, Anna
datacite.contributor.supervisoreditor: DeLuca, Jennifer G
dc.contributor.orcidConti, Duccio [0000-0003-4009-5940]
dc.contributor.orcidDraviam, Viji M [0000-0001-8295-3689]
dc.identifier.eissn2050-084X
pubs.funder-project-idQueen Mary University of London (SBC8DRA2)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (R01003X/1)
pubs.funder-project-idCancer Research UK (C28598/A9787)
pubs.funder-project-idMedical Research Council (MR/K50127X/1)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)