Accurate chromosome segregation is required for propagation of all cells. Errors in this process are implicated in oncogenesis, birth defects and cell death. Crucial to proper partitioning of the chromosomes during cell division is the establishment, arrangement and then breakdown of a bipolar spindle.
The aim of this grant is to further understand the structure, assembly and dynamics of the proteins that create and control the organization of the spindle in the model organism Saccharomyces cerevisiae. The microtubule organizing center in yeast is the spindle pole body (SPB). The SPB is a dynamic structure that undergoes remodeling in a cell-cycle specific manner. We have identified proteins involved in the remodeling process and will characterize them. We have provided a detailed architectural description of the SPB and will continue our structural analysis. The SPB nucleates and organizes microtubules. We will perform a set of experiments designed to distinguish between two current models for nucleation. Finally, we have found that kinetochores can biorient without being attached to the plus-end of microtubules. New insights into biorientation will be obtained from determining the role of kinetochores, motors and other spindle proteins in the formation of the bipolar spindle when plus-end attachment is not involved. Because many proteins and spindle features are conserved from yeast to human, our studies will inform models of how eukaryotic cells correctly distribute their genetic material.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040506-21
Application #
7762200
Study Section
Nuclear Dynamics and Transport (NDT)
Program Officer
Deatherage, James F
Project Start
1988-07-01
Project End
2011-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
21
Fiscal Year
2010
Total Cost
$438,689
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Umbreit, Neil T; Miller, Matthew P; Tien, Jerry F et al. (2014) Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation. Nat Commun 5:4951

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