The chromatin remodeller RSF1 is essential for PLK1 deposition and function at mitotic kinetochores.

Accumulation of PLK1 at kinetochores is essential for chromosome alignment and segregation; however, the mechanism underlying PLK1 recruitment to kinetochores remains unresolved. The chromatin remodeller RSF1 tightly associates with centromere proteins, but its mitotic function is unknown. Here we show that RSF1 localizes at mitotic kinetochores and directly binds PLK1. ...
RSF1 depletion disrupts localization of PLK1 at kinetochores; the C-terminal fragment of RSF1, which can bind PLK1, is sufficient to restore PLK1 localization. Moreover, CDK1 phosphorylates RSF1 at Ser1375, and this phosphorylation is necessary for PLK1 recruitment. Subsequently, PLK1 phosphorylates RSF1 at Ser1359, stabilizing PLK1 deposition. Importantly, RSF1 depletion mimicks the chromosome misalignment phenotype resulting from PLK1 knockdown; these defects are rescued by RSF1 S1375D or RSF1 S1359D but not RSF1 S1375A, showing a functional link between phosphorylation of RSF1 and chromosome alignment. Together, these data show that RSF1 is an essential centromeric component that recruits PLK1 to kinetochores and plays a crucial role in faithful cell division.
Mesh Terms:
Amino Acid Sequence, CDC2 Protein Kinase, Cell Cycle Proteins, Cyclin-Dependent Kinases, Gene Knockout Techniques, HeLa Cells, Humans, Kinetochores, Mitosis, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins, Trans-Activators
Nat Commun
Date: Aug. 10, 2015
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