Journal
EMBO JOURNAL
Volume 37, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/embj.201797677
Keywords
CENP-B; chromosomal passenger complex; heterochromatin protein 1; histone H3S10 phosphorylation
Categories
Funding
- Wellcome Trust [107022, 202811]
- Wellcome Trust Centre [077707, 092076]
- Wellcome Trust Multi User Equipment Grant [WT104915MA]
- JSPS KAKENHI [JP15K21730, JP25116005, JP26291071]
- Kato Memorial Bioscience Foundation
- Takeda Science Foundation
- Marie Curie Action PloidyNet - European Union Seventh Framework Programme (FP7) [607722]
- Grants-in-Aid for Scientific Research [15K21730, 26291071, 25116005, 16K18494] Funding Source: KAKEN
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The chromosomal passenger complex (CPC) is directed to centromeres during mitosis via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1 alpha (HP1 alpha) influences CPC localisation and function during mitotic entry is less clear. Here, we alter HP1 dynamics by fusing it to a CENP-B DNA-binding domain. Tethered HP1 strongly recruits the CPC, destabilising kinetochore-microtubule interactions and activating the spindle assembly checkpoint. During mitotic exit, the tethered HP1 traps active CPC at centromeres. These HP1-CPC clusters remain catalytically active throughout the subsequent cell cycle. We also detect interactions between endogenous HP1 and the CPC during G(2). HP1 alpha and HP1 gamma cooperate to recruit the CPC to active foci in a CDK1-independent process. Live cell tracking with Fab fragments reveals that H3S10ph appears well before H3T3 is phosphorylated by Haspin kinase. Our results suggest that HP1 may concentrate and activate the CPC at centromeric heterochromatin in G(2) before Aurora B-mediated phosphorylation of H3S10 releases HP1 from chromatin and allows pathways dependent on H3T3ph and Sgo1 to redirect the CPC to mitotic centromeres.
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