Centromeric association of polo kinase Cdc5 regulates kinetochore structure and chromosome stability

Authors

• PK Mishra
• L Boeckmann
• T Pachpor
• WC Au
• S Ciftci
• LE Dittman
• Z Jowhar
• S Azeem
• L Bursch
• D D’Amours
• RE Baker
• E Yeh
• K Bloom
• MA Basrai

Abstract

High fidelity chromosome segregation is essential for normal cell proliferation because errors in this process contribute to aneuploidy, birth defects and cancer. The kinetochore (centromeric DNA and associated proteins) is essential for faithful chromosome segregation. An evolutionarily conserved histone H3 variant Cse4 (CENP-A in humans) is an epigenetic determinant for the structure and function of the kinetochore and is a component of specialized centromere (CEN)-specific nucleosomes. Here we report that an evolutionarily conserved polo-like kinase Cdc5 (Plk1 in humans) associates with centromeres in a cell cycle dependent manner with maximum enrichment observed in mitotic cells. Cdc5 interacts in vivo with Cse4, and phosphorylates Cse4 in vitro. Consistent with these observations, the levels of CEN-associated Cse4 are reduced in cdc5 mutants. We further show that Cdc5 is required for the structural integrity of CEN chromatin and faithful chromosome segregation. Genetic alterations of Plk1Cdc5 have been observed in several cancers, however the biological relevance of these observations is not well understood. Our results have uncovered a novel role for Cdc5 in maintaining the integrity of CEN chromatin to facilitate faithful chromosome segregation.

Scientific Focus Area: Chromosome Biology

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