Chromosome movement is essential to genome segregation upon cell division. Active force generation at the kinetochore by both microtubule-based motor proteins and microtubule dynamics is thought to power chromosome movement. How do spindle forces oppose kinetochore-based forces to specify that chromosomes, instead of microtubules, move? To answer this question, one must uncover the contribution of spindle mechanical architecture to chromosome movement.
In Aim #1, we will determine how the spindle exerts force on kinetochore-microtubules to oppose kinetochore-based forces and thereby impose chromosome movement.
In Aim #2, we will determine how these spindle forces on kinetochore-microtubules are dynamically maintained during continuous spindle reorganization and molecule turnover, as well as external insults. Together, our results will provide insight into how the load of chromosome movement is born by such a dynamic machine as the spindle.
Cell division is responsible for reproduction, growth, development, and continuous organism renewal and repair. During cell division, chromosomes must be accurately segregated as errors can lead to cancer and birth defects. The results of this study will provide mechanical insight into how chromosomes are moved by the cell, and may as such provide new targets for cancer therapeutics.
|Elting, Mary Williard; Prakash, Manu; Udy, Dylan B et al. (2017) Mapping Load-Bearing in the Mammalian Spindle Reveals Local Kinetochore Fiber Anchorage that Provides Mechanical Isolation and Redundancy. Curr Biol 27:2112-2122.e5|
|Kuhn, Jonathan; Dumont, Sophie (2014) Imaging and physically probing kinetochores in live dividing cells. Methods Cell Biol 123:467-87|
|Dumont, Sophie (2014) Spindle size: small droplets and a big step forward. Curr Biol 24:R116-8|