This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cells have surveillance systems called checkpoints that monitor DNA damage and DNA replication stress. Exposure of cells to genotoxic agents such as hydroxyurea (HU) activates replication checkpoint that slows down or stalls DNA replication. Several checkpoint proteins interact among themselves to monitor replication defects and activate repair processes to maintain DNA integrity. HU treatment of cells also causes actin depolymerization, and Swe1 accumulation that monitors cells shape and growth through morphogenesis checkpoint. Approximately 300 genes from various pathways have been found to confer HU resistance and monitor cell growth and viability. However, less is known about the mechanisms of their action and the interactions among these genes to confer resistance to HU. The single inositol phosphosphingolipid phospholipase C gene ISC1 of S. cerevisiae confers resistance to HU and MMS. Deletion of ISC1 causes G2/M arrest in HU and this defect can be overcome upon deletion of SWE1 gene. In addition, genome-wide analyses have shown that ISC1 gene genetically interacts with DNA replication/sister-chromatid cohesion genes CSM3, CTF4, CTF8 and CTF18. Our goal is to understand the mechanism of action of Isc1 in cellular integrity upon exposure to replication stress agents and also its interaction with the DNA replication/ sister-chromatid cohesion genes to maintain cell growth and viability.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017677-10
Application #
8360381
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
2011-07-01
Project End
2012-07-18
Budget Start
2011-07-01
Budget End
2012-07-18
Support Year
10
Fiscal Year
2011
Total Cost
$144,546
Indirect Cost
Name
Medical University of South Carolina
Department
Biochemistry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
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