Report

Histone H3 Thr-3 Phosphorylation by Haspin Positions Aurora B at Centromeres in Mitosis

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Science  12 Aug 2010:
1189435
DOI: 10.1126/science.1189435

Abstract

Aurora-B is a component of the chromosomal passenger complex (CPC) required for correct spindle-kinetochore attachments during chromosome segregation and for cytokinesis. The chromatin factors that recruit the CPC to centromeres are unknown, however. Here, we show that phosphorylation of histone H3 threonine-3 (H3T3ph) by Haspin is necessary for CPC accumulation at centromeres, and that the CPC subunit Survivin binds directly to H3T3ph. A nonbinding Survivin-D70A/D71A mutant does not support centromeric CPC concentration, and both Haspin depletion and Survivin-D70A/D71A mutation diminish centromere localization of MCAK and mitotic checkpoint signaling in taxol. Survivin-D70A/D71A mutation and microinjection of H3T3ph-specific antibody both compromise centromeric Aurora-B functions but do not prevent cytokinesis. Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora-B during mitosis.