Mitosis, or the separation of chromosomes during cell division, is driven by dynamic interactions between the kinetochore region on chromosomes and string-like structures called microtubules. A number of proteins, including the enzyme Cdk1, regulate these interactions, but it is unclear what kinetochore components such enzymes work upon.
Kathy Gould and colleagues have identified the kinetochore protein Nsk1 as a novel substrate for Cdk1 and have characterized its role in kinetochore-microtubule interactions. They show Nsk1 promotes proper interactions between the kinetochore and microtubules; therefore, cells lacking Nsk1 show errors in chromosome segregation. Nsk1’s role in this process is regulated by addition of phosphate groups (phosphorylation). Mutant Nsk1 (which can’t be phosphorylated) binds prematurely to kinetochores and spindle, and leads to even more severe defects in mitosis.
The results reported in the Nov. 14 issue of the Journal of Cell Biology establish new roles for these proteins in ensuring appropriate chromosome segregation during cell division.
The research was supported by grants from the National Cancer Institute, the National Institute of General Medical Sciences, the Howard Hughes Medical Institute and the American Lebanese Syrian Associated Charities.