HP1α targets the chromosomal passenger complex for activation at heterochromatin before mitotic entry

The EMBO Journal
Jan G RuppertWilliam C Earnshaw

Abstract

The chromosomal passenger complex (CPC) is directed to centromeres during mitosis via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1α (HP1α) influences CPC localisation and function during mitotic entry is less clear. Here, we alter HP1α 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 G2 HP1α and HP1γ 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 G2 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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Citations

Feb 10, 2019·Biomolecules·Margarida Moura, Carlos Conde
Sep 19, 2019·The Journal of Cell Biology·Mary Kate BonnerAlexander E Kelly
Oct 2, 2019·The Journal of Cell Biology·Maria A AbadA Arockia Jeyaprakash
Jan 30, 2020·Cell Cycle·M Lienhard SchmitzMarkus Seibert
May 28, 2019·Cell Cycle·Monique M WilliamsRaul A Urrutia
Sep 17, 2020·Journal of Cell Science·Takaaki TsunematsuYasusei Kudo
Jul 5, 2018·Frontiers in Cell and Developmental Biology·Adrian T Saurin
Jan 15, 2021·The Journal of Cell Biology·Marina Murillo-PinedaLars E T Jansen
Apr 10, 2021·The Journal of Cell Biology·Lin-Ing WangKim S McKim

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Methods Mentioned

BETA
transfection
fluorescence microscopy
fluorescence recovery after photobleaching
flow cytometry
PCR
flow

Software Mentioned

SoftWoRx
AutoQuant X3
OMERO
Geneart
Image
Pro Premier
Fiji
CellProfiler
FlowJo
Clustal Omega

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