The long-term objectives are to identify and study the different repair pathways used by cells to avoid spontaneous mitotic DNA damage, chromosome loss and mitotic recombination, using the yeast Saccharomyces cerevisiae as a model system for genetic and molecular studies. Chromosome loss and mitotic recombination lead to loss of heterozygosity (LOH), events that are associated with human disease and neoplastic growth of cells. Spontaneous DNA damage often leads to stalling of replication forks. Replication is resumed by repairing the blocking lesion, or bypass of the lesion. Bypass can involves recombination processes or post-replication repair (PRR). The components of these pathways and how they are integrated will be studied. There are three main areas of investigation that are proposed: 1) the contribution of recombination repair genes and DNA damage checkpoint functions to genomic stability, 2) the role of the PRR genes to genomic stability and overlap with the recombination repair functions, and 3) the role that sister chromatid cohesion plays in determining the type of repair pathway used to overcome replication fork stalling and spontaneous DNA damage repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM070711-01
Application #
6761624
Study Section
Genetics Study Section (GEN)
Program Officer
Anderson, Richard A
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$372,177
Indirect Cost
Name
New York University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Klein, Hannah L (2008) The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair (Amst) 7:686-93