Dynamic phosphorylation of HP1 alpha regulates mitotic progression in human cells

摘要

Heterochromatin protein 1 alpha (HP1 alpha), a key player in the establishment and maintenance of higher-order chromatin regulates key cellular processes, including metaphase chromatid cohesion and centromere organization. However, how HP1a controls these processes is not well understood. Here we demonstrate that post-translational modifications of HP1a dictate its mitotic functions. HP1a is constitutively phosphorylated within its amino terminus, whereas phosphorylation within the hinge domain occurs preferentially at G2/M phase of the cell cycle. The hinge-phosphorylated form of HP1a specifically localizes to kinetochores during early mitosis and this phosphorylation mediated by NDR1 kinase is required for mitotic progression and for Sgo1 binding to mitotic centromeres. Cells lacking NDR kinase show loss of mitosis-specific phosphorylation of HP1a leading to prometaphase arrest. Our results reveal that NDR kinase catalyses the hinge-specific phosphorylation of human HP1a during G2/M in vivo and this orchestrates accurate chromosome alignment and mitotic progression.