Homologous recombination repair (HRR) eliminates deleterious chromosome lesions and is therefore critical for the maintenance of genome stability. In humans, defects in HRR lead to the tumor phenotype. Studies conducted during the last funding cycle have led to major advances in understanding HRR proteins and mechanisms. Capitalizing on this past success, a combinatorial approach encompassing structural, biochemical, and biological studies will be employed to delineate the integrated roles that several tumor suppressor proteins play in the HRR pathway. The results from this project will allow us to formulate detailed models of HRR mechanisms in human cells. Given the importance of HRR in tumor suppression and in the removal of DNA crosslinks induced by chemotherapeutic agents, our studies have direct relevance to cancer biology and to the development of molecules to evaluate the potential of HRR pathway-targeted therapeutic strategies. As in the past, we will rely on the EMB-ML and SCB cores for their expertise and services. Importantly, our studies will create significant synergy with Projects 2, 3, 5 and 6 and draw links to the entire program, and will thus enhance the impact and significance of our research findings. We anticipate our investigations to help drive the search for connections among HRR and other DNA repair pathways and thereby enable the SBDR program to remain at the frontier of understanding the integrated cellular response to damaged DNA.

Public Health Relevance

Failure to repair damaged chromosome compromises the integrity of the genome and can lead to cancer formation. The proposed studies will delineate the role of several tumor suppressors and their partner proteins in the homologous recombinational repair of DNA double-strand breaks. The results will have direct relevance to understanding the role of DNA repair in cancer biology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA092584-13
Application #
8567646
Study Section
Special Emphasis Panel (ZCA1-RPRB-0)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
13
Fiscal Year
2013
Total Cost
$401,289
Indirect Cost
$122,659
Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
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