Loss of genetic integrity is a critical factor in the process of malignant transformation and developing resistance of tumors to anti-cancer agents. Genetic instability often is a result of non-functional checkpoint controls. Therefore, understanding the mechanisms of checkpoint controls is of great importance. The S-phase checkpoint coordinates progression of the cell cycle with DNA replication. One critical issue concerns the mechanism regulating the S-phase checkpoint. In S. cerevisiae, progression into mitosis is regulated in part by transcriptional activation of a component of the anaphase promoting complex, Cdc20p. Recent evidence strongly suggests that S-phase checkpoint proteins, Rad23p and Ddi1p delay mitosis in response to a DNA replication block through silencing of CDC20. This proposal focuses on a detailed analysis of the role that Rad23p and Ddi1p play in regulation of CDC20 expression, as well the mechanism of their activation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM068257-02
Application #
6726793
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Wolfe, Paul B
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037