Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation.
dc.contributor.author | Conti, Duccio | |
dc.contributor.author | Gul, Parveen | |
dc.contributor.author | Islam, Asifa | |
dc.contributor.author | Martín-Durán, José M | |
dc.contributor.author | Pickersgill, Richard W | |
dc.contributor.author | Draviam, Viji M | |
dc.date.accessioned | 2019-12-25T05:10:03Z | |
dc.date.available | 2019-12-25T05:10:03Z | |
dc.date.issued | 2019-12-06 | |
dc.date.submitted | 2019-06-14 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.other | 49325 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/300252 | |
dc.description | Funder: Islamic Development Bank; FundRef: http://dx.doi.org/10.13039/501100003971 | |
dc.description.abstract | Microtubules 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.language | en | |
dc.publisher | eLife Sciences Publications, Ltd | |
dc.rights | Attribution 4.0 International (CC BY 4.0) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Research Article | |
dc.subject | Cell Biology | |
dc.subject | kinetochore | |
dc.subject | microtubule | |
dc.subject | mitosis | |
dc.subject | chromosome | |
dc.subject | Human | |
dc.title | Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation. | |
dc.type | Article | |
dc.date.updated | 2019-12-25T05:10:02Z | |
prism.publicationName | Elife | |
dc.identifier.doi | 10.17863/CAM.47325 | |
dcterms.dateAccepted | 2019-12-01 | |
rioxxterms.versionofrecord | 10.7554/eLife.49325 | |
rioxxterms.version | VoR | |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | |
datacite.contributor.supervisor | senior_editor: Akhmanova, Anna | |
datacite.contributor.supervisor | editor: DeLuca, Jennifer G | |
dc.contributor.orcid | Conti, Duccio [0000-0003-4009-5940] | |
dc.contributor.orcid | Draviam, Viji M [0000-0001-8295-3689] | |
dc.identifier.eissn | 2050-084X | |
pubs.funder-project-id | Queen Mary University of London (SBC8DRA2) | |
pubs.funder-project-id | Biotechnology and Biological Sciences Research Council (R01003X/1) | |
pubs.funder-project-id | Cancer Research UK (C28598/A9787) | |
pubs.funder-project-id | Medical Research Council (MR/K50127X/1) | |
cam.issuedOnline | 2019-12-06 |
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