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dc.contributor.authorWang, Fangwei
dc.contributor.authorUlyanova, Natalia P.
dc.contributor.authorDaum, John R.
dc.contributor.authorPatnaik, Debasis
dc.contributor.authorKateneva, Anna V.
dc.contributor.authorGorbsky, Gary J.
dc.contributor.authorHiggins, Jonathan Michael Gregory
dc.date.accessioned2013-10-17T21:24:45Z
dc.date.issued2012
dc.identifier.citationWang, Fangwei, Natalia P. Ulyanova, John R. Daum, Debasis Patnaik, Anna V. Kateneva, Gary J. Gorbsky, and Jonathan M.G. Higgins. 2012. Haspin inhibitors reveal centromeric functions of aurora b in chromosome segregation. The Journal of Cell Biology 199(2): 251-268.en_US
dc.identifier.issn0021-9525en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181055
dc.description.abstractHaspin phosphorylates histone H3 at threonine-3 (H3T3ph), providing a docking site for the Aurora B complex at centromeres. Aurora B functions to correct improper kinetochore–microtubule attachments and alert the spindle checkpoint to the presence of misaligned chromosomes. We show that Haspin inhibitors decreased H3T3ph, resulting in loss of centromeric Aurora B and reduced phosphorylation of centromere and kinetochore Aurora B substrates. Consequently, metaphase chromosome alignment and spindle checkpoint signaling were compromised. These effects were phenocopied by microinjection of anti-H3T3ph antibodies. Retargeting Aurora B to centromeres partially restored checkpoint signaling and Aurora B–dependent phosphorylation at centromeres and kinetochores, bypassing the need for Haspin activity. Haspin inhibitors did not obviously affect phosphorylation of histone H3 at serine-10 (H3S10ph) by Aurora B on chromosome arms but, in Aurora B reactivation assays, recovery of H3S10ph was delayed. Haspin inhibitors did not block Aurora B localization to the spindle midzone in anaphase or Aurora B function in cytokinesis. Thus, Haspin inhibitors reveal centromeric roles of Aurora B in chromosome movement and spindle checkpoint signaling.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1083/jcb.201205106en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471242/pdf/en_US
dash.licenseLAA
dc.subjectArticleen_US
dc.titleHaspin inhibitors reveal centromeric functions of Aurora B in chromosome segregationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of Cell Biologyen_US
dash.depositing.authorHiggins, Jonathan Michael Gregory
dc.date.available2013-10-17T21:24:45Z
dc.identifier.doi10.1083/jcb.201205106*
dash.contributor.affiliatedHiggins, Jonathan Michael Gregory


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