Phosphorylation-dephosphorylation cycle of HP1α governs accurate mitotic progression

Heterochromatin protein 1 alpha (HP1 alpha), a bona fide factor of silent chromatin, is required for establishing as well as maintaining the higher-order chromatin structure in eukaryotes. HP1 alpha is decorated with several post-translational modifications, and many of these are critical for its cellular functions. HP1 alpha is heavily phosphorylated; however, its physiological relevance had remained to be completely understood. We have recently demonstrated that human HP1 alpha is a mitotic target for NDR kinase, and the phosphorylation at the hinge region of HP1 alpha at the G(2)/M phase of the cell cycle is crucial for mitotic progression and Sgo1 loading at mitotic centromeres (Chakraborty et al., 2014). We now demonstrate that the dephosphorylation of HP1 alpha within its hinge domain occurs during mitosis, specifically soon after prometaphase. In the absence of the hinge-specific HP1 alpha phosphorylation, either as a consequence of depleting NDR1 or in cells expressing a non-phosphorylatable HP1 alpha mutant, the cells arrest in prometaphase with several mitotic defects. In this study we show that NDR1-depleted cells expressing hinge-specific phosphomimetic HP1 alpha mutant rescues the prometaphase arrest but displays defects in mitotic exit, suggesting that the dephosphorylation of HP1 alpha is required for the completion of cytokinesis. Taken together, our results reveal that the phosphorylation-dephosphorylation cycle of HP1 alpha orchestrates accurate progression of cells through mitosis.