NIH Research Festival
Evolutionarily conserved polo-like kinase, Cdc5 (Plk1 in humans) associates with kinetochores during mitosis, and facilitates the removal of centromeric cohesin. However, physiological significance for the mitotic association of Cdc5 with the kinetochore is not fully understood. Here we report that Cse4 is a novel substrate for polo-like kinase Cdc5, and show that Cdc5-mediated phosphorylation of Cse4 is required for faithful chromosome segregation. We determined that Cdc5 interacts with Cse4 in vivo and this interaction is cell cycle regulated, which only observed in mitotic cells. In vitro kinase assays show that Cdc5 phosphorylates Cse4, and mass spectrometry analysis identified nine phosphorylated serine residues clustered within the N-terminus of Cse4. Non-phosphorylatable cse4-9SA exhibits increased errors in chromosome segregation, reduced levels of centromere-associated Mif2, and Mcd1/Scc1 when combined with a deletion of MCM21. Moreover, the loss of Cdc5 from the centromeric chromatin causes defects in kinetochore integrity and reduced levels of centromere-associated Cse4. The cell cycle regulated association of Cdc5 with Cse4 is essential for cell viability as constitutive association of Cdc5 with Cse4 at the kinetochore causes defects in cell growth. In summary, our results have defined a novel role for Cdc5-mediated Cse4 phosphorylation in faithful chromosome segregation and kinetochore function.
Scientific Focus Area: Chromosome Biology
This page was last updated on Friday, March 26, 2021