Genomic instability is a hallmark of cancer cells. The spindle checkpoint ensures genomic integrity by inhibiting anaphase onset if even a single chromosome is not properly aligned on the spindle. Recent evidence suggests that defects in mammalian homologues of the yeast checkpoint genes may contribute to the generation of human cancer. The long-term objective of this application is to understand the molecular mechanisms that coordinate cell cycle processes to ensure accurate cell division in mammalian cells.
The specific aims of this proposal are: (1) to determine if an intrinsic timing component contributes to proper order of the cell cycle, (2) to determine if checkpoint proteins are essential for normal cell division, and (3) to determine the molecular interaction among checkpoint proteins and regulations of anaphase.
These aims will be addressed in cultured cells with live cell imaging in combination with in vitro studies using immunoprecipitation and affinity chromatography. Chromophore- assisted-laser inactivation (CALI) of immunoprecipitation and affinity chromatography. Chromophore-assisted-laser inactivation (CALI) of protein function will be used to produce """"""""cellular knockouts"""""""" of checkpoint proteins. The focus of the protein function will be used to produce """"""""cellular knockouts"""""""" of checkpoint proteins. The focus of the biochemical studies will be molecular interactions of human Mad1 with other checkpoint proteins and regulators of anaphase. These studies will contribute to our understanding of the mechanisms employed by mammalian cells to prevent inaccurate chromosome segregation and maintain genomic integrity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020756-02
Application #
6385265
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Wolfe, Paul B
Project Start
2000-04-01
Project End
Budget Start
2001-04-01
Budget End
2001-12-31
Support Year
2
Fiscal Year
2001
Total Cost
$32,747
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117