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dc.contributor.authorBury, Len
dc.contributor.authorCoelho, PAen
dc.contributor.authorSimeone, Aen
dc.contributor.authorFerries, Sen
dc.contributor.authorEyres, CEen
dc.contributor.authorEyres, PAen
dc.contributor.authorZernicka-Goetz, Magdalenaen
dc.contributor.authorGlover, Daviden
dc.date.accessioned2017-10-04T11:10:21Z
dc.date.available2017-10-04T11:10:21Z
dc.identifier.issn0021-9525
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/267707
dc.description.abstractEstablishing the bipolar spindle in mammalian oocytes after their prolonged arrest is crucial for meiotic fidelity and subsequent development. In contrast to somatic cells, the first meiotic spindle assembles in the absence of centriole-containing centrosomes. Ran-GTP can promote microtubule nucleation near chromatin, but additional unidentified factors are postulated for the activity of multiple acentriolar microtubule organizing centers in the oocyte. We now demonstrate that partially overlapping, nonredundant functions of Aurora A and Plk4 kinases contribute to initiate acentriolar meiosis I spindle formation. Loss of microtubule nucleation after simultaneous chemical inhibition of both kinases can be significantly rescued by drug-resistant Aurora A alone. Drug-resistant Plk4 can enhance Aurora A–mediated rescue, and, accordingly, Plk4 can phosphorylate and potentiate the activity of Aurora A in vitro. Both kinases function distinctly from Ran, which amplifies microtubule growth. We conclude that Aurora A and Plk4 are rate-limiting factors contributing to microtubule growth as the acentriolar oocyte resumes meiosis.
dc.description.sponsorshipL. Bury was the recipient of a Cancer Research UK research studentship from Cambridge Cancer Centre. P.A. Coelho is supported by Cancer Research UK program grant C3/A18795 to D.M. Glover. M. Zernicka-Goetz is a Wellcome Trust Senior Fellow. P.A. Eyers acknowledges North West Cancer Research for additional support (grants CR1037 and CR1088).
dc.publisherRockefeller University Press
dc.rightsAttribution 4.0 International*
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titlePlk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytesen
dc.typeArticle
prism.publicationNameThe Journal of Cell Biologyen
dc.identifier.doi10.17863/CAM.13637
dcterms.dateAccepted2017-08-09en
rioxxterms.versionofrecord10.1083/jcb.201606077en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-08-09en
dc.contributor.orcidZernicka-Goetz, Magdalena [0000-0002-7004-2471]
dc.contributor.orcidGlover, David [0000-0003-0956-0103]
dc.identifier.eissn1540-8140
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (CRUK-A18795)
cam.issuedOnline2017-09-28en


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