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dc.contributor.authorSong, Xinhong
dc.contributor.authorConti, Duccio
dc.contributor.authorShrestha, Roshan L
dc.contributor.authorBraun, Dominique
dc.contributor.authorDraviam, Viji M
dc.date.accessioned2022-01-28T14:44:23Z
dc.date.available2022-01-28T14:44:23Z
dc.date.issued2021-12-01
dc.identifier.issn2041-1723
dc.identifier.other34853300
dc.identifier.otherPMC8636589
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333073
dc.description.abstractDefects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101528555
dc.sourceessn: 2041-1723
dc.subjectChromosomes
dc.subjectKinetochores
dc.subjectMicrotubules
dc.subjectGenomic Instability
dc.subjectResorcinols
dc.subjectAlcian Blue
dc.subjectPhenazines
dc.subjectPhenothiazines
dc.subjectCDC2 Protein Kinase
dc.subjectReceptors, Neuropeptide Y
dc.subjectChromosome Segregation
dc.subjectCyclin B1
dc.subjectSpindle Apparatus
dc.subjectAurora Kinase B
dc.subjectSpindle Poles
dc.titleCounteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.
dc.typeArticle
dc.date.updated2022-01-28T14:44:22Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.80497
dcterms.dateAccepted2021-11-02
rioxxterms.versionofrecord10.1038/s41467-021-27131-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidConti, Duccio [0000-0003-4009-5940]
dc.contributor.orcidDraviam, Viji M [0000-0001-8295-3689]
dc.identifier.eissn2041-1723
pubs.funder-project-idRCUK | Biotechnology and Biological Sciences Research Council (BB/T017716/1, BB/W002698/1, R01003X/1)
pubs.funder-project-idQueen Mary University of London (SBC9DRA2)
pubs.funder-project-idCancer Research UK (C28598/A9787)
pubs.funder-project-idMedical Research Council (MR/K50127X/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/T017716/1, R01003X/1, BB/W002698/1)
cam.issuedOnline2021-12-01


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