Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis.
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 the kinesin MCAK and the mitotic checkpoint response to 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.
PubMed ID: 20705812
PMC ID: PMC2967368
Article link: Science.
Grant support: R01-GM050412 NIGMS NIH HHS , R01-GM063045 NIGMS NIH HHS , R01-GM074210 NIGMS NIH HHS , R01 GM074210-04 NIGMS NIH HHS , R01 GM050412-16 NIGMS NIH HHS , R01 GM063045-10 NIGMS NIH HHS , R01 GM050412-18 NIGMS NIH HHS , R01 GM050412 NIGMS NIH HHS , R01 GM063045 NIGMS NIH HHS , R01 GM074210 NIGMS NIH HHS
Genes referenced: aurkb birc5.1 kif2c