. This proposal will use a yeast model system to explore a checkpoint that coordinates completion of DNA replication with mitosis. Specifically, this proposal will investigate how a yeast cell, sensing that replication is not yet complete, blocks the transition from metaphase to anaphase. The importance of this checkpoint is obvious, in that entry into the process of cell division prior to duplication of the genetic material is a catastrophic event, leading to instantaneous loss of genomic integrity. The proposal focuses on several conserved proteins that were identified through genetic analysis, some of which previously had not been associated with checkpoint functions.
The specific aims are to characterize the parameters of a """"""""late"""""""" S phase checkpoint that depends on Pds1 to delay anaphase, to investigate the role of Rad23 and Ddi1 in the Pds1-dependent S phase checkpoint and to engage in a detailed structure/function analysis of the Rad23 and Ddi1 proteins.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA085487-03
Application #
6522577
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Spalholz, Barbara A
Project Start
2000-09-30
Project End
2004-09-29
Budget Start
2002-09-30
Budget End
2003-09-29
Support Year
3
Fiscal Year
2002
Total Cost
$277,800
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Wohlschlegel, James A; Johnson, Erica S; Reed, Steven I et al. (2004) Global analysis of protein sumoylation in Saccharomyces cerevisiae. J Biol Chem 279:45662-8
Andrews, Catherine A; Segal, Marisa; Reed, Steven I et al. (2004) Cdc20 in S-phase: the Banquo at replication's banquet. Cell Cycle 3:276-9
Clarke, Duncan J; Segal, Marisa; Andrews, Catherine A et al. (2003) S-phase checkpoint controls mitosis via an APC-independent Cdc20p function. Nat Cell Biol 5:928-35
Bertolaet, B L; Clarke, D J; Wolff, M et al. (2001) UBA domains mediate protein-protein interactions between two DNA damage-inducible proteins. J Mol Biol 313:955-63