The broad long-term objective is to understand the process of chromosome segregation during eukaryotic cell division. Inaccurate chromosome segregation leads to genetic instability. Down syndrome is the most frequent genetic defect in infants and cancer will kill one American in four. Both are conditions caused by genetic instability and it is possible that lesions in the spindle checkpoint cause meiotic chromosome loss in Down syndrome and chromosome loss and gain in many tumors. The primary focus within the proposal is the study of the molecular mechanism by which chromosomes signal to stop cell cycle progression in response to mitotic spindle damage in budding yeast. The first specific aim is to identify the components of the complex that inhibit Cdc20p-APC activity in response to spindle damage. The second specific aim is to identify the kinetochore sensor necessary for activating the checkpoint signal complex. To achieve these ends, yeast molecular genetics coupled with classical protein biochemistry shall be employed. When used in combination these methods have been shown to be powerful tools for exploring the molecular roles of protein complexes. The hope is that understanding the molecular mechanism of the spindle checkpoint in budding yeast will help us to understand its role in human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067509-01A1
Application #
6690854
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Wolfe, Paul B
Project Start
2003-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Barnhart, Erin L; Dorer, Russell K; Murray, Andrew W et al. (2011) Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis. Mol Biol Cell 22:2448-57