Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation

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Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation

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Title: Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation
Author: Wang, Fangwei; Ulyanova, Natalia P.; Daum, John R.; Patnaik, Debasis; Kateneva, Anna V.; Gorbsky, Gary J.; Higgins, Jonathan Michael Gregory

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Citation: Wang, 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.
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Abstract: Haspin 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.
Published Version: doi:10.1083/jcb.201205106
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471242/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181055
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