|Awarded On||November 19, 2015|
|Title||Structural and Functional Analyses of the Spindle Checkpoint|
|Award Mechanism||Individual Investigator|
|Institution/Organization||The University of Texas Southwestern Medical Center|
|Principal Investigator/Program Director||Xuelian Luo|
|Cancer Sites||All Sites|
The spindle checkpoint ensures the fidelity of chromosome segregation during mitosis and meiosis. Studies in mouse models have firmly established that malfunction of the spindle checkpoint leads to chromosome missegregation and aneuploidy, which can result in tumorigenesis, premature aging, and other defects. Several spindle checkpoint genes, including Bub1, are mutated in human cancers, albeit with low frequency. Their expression is regulated by tumor suppressors and oncogenes and is frequently altered in cancer cells. This proposal investigates the basic molecular mechanisms of chromosome segregation in human cells, with a focus on the enigmatic roles and regulation of the checkpoint k...