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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Transition Award (R00)
Project #
5R00GM094335-05
Application #
8708894
Study Section
Special Emphasis Panel (NSS)
Program Officer
Deatherage, James F
Project Start
2010-09-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$249,001
Indirect Cost
$76,234
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Dentistry
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dumont, Sophie (2014) Spindle size: small droplets and a big step forward. Curr Biol 24:R116-8