The Project (Homologous Recombination and Crosslink Repair) integrates into the SBDR Program Project by focusing upon the lesion removal step of the overall cellular response to DMA double strand breaks and interstrand crosslinks. Genetic studies have shown a pivotal role of homologous recombination in double-strand break and crosslink repair pathways. There is ample evidence that homologous recombination repair (HRR) and companion DNA damage signaling reactions are critical for genome maintenance. Deregulation of these biological pathways leads to several cancers and diseases predisposing to cancer, including familial breast and ovarian cancers (BRCA1 and BRCA2), Fanconi anemia (FANCD2 and BRCA2), and Ataxia telangiectasia (ATM). As with other DNA repair systems, HRR entails extensive protein-protein and protein-ligand interactions. Our research project strives to decipher the molecular basis of the hierarchy of interactions that modulate the efficiency of HRR and crosslink removal. To achieve our objectives, collaborative studies described under four Aims will be carried out. Specifically, we will (1) determine the molecular basis of the Rad52 recombination mediator activity needed for Rad51 presynaptic filament assembly, (2) delineate the significance of the interactions of Rad51 with Pir51 and also BRCA2 Exon 27, (3) examine the biochemical interaction between FANCD2 and ATM and define the role of FANCD2 in Rad51-mediated reactions, and (4) determine the basis for complex assemblies involving BARD1 and its partner proteins and define the influence of the BRCA1- BARD1 complex on the Rad51 recombinase activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA092584-09
Application #
7924237
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
9
Fiscal Year
2009
Total Cost
$484,262
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
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