The Project (Homologous Recombination and Crosslink Repair) integrates into the SBDR ProgramProject by focusing upon the lesion removal step of the overall cellular response to DMA doublestrand breaks and interstrand crosslinks. Genetic studies have shown a pivotal role of homologousrecombination in double-strand break and crosslink repair pathways. There is ample evidence thathomologous recombination repair (HRR) and companion DNA damage signaling reactions arecritical for genome maintenance. Deregulation of these biological pathways leads to severalcancers 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-ligandinteractions. Our research project strives to decipher the molecular basis of the hierarchy ofinteractions 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 Rad51presynaptic filament assembly, (2) delineate the significance of the interactions of Rad51 with Pir51and also BRCA2 Exon 27, (3) examine the biochemical interaction between FANCD2 and ATM anddefine the role of FANCD2 in Rad51-mediated reactions, and (4) determine the basis for complexassemblies 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 #
2P01CA092584-06
Application #
7152386
Study Section
Subcommittee G - Education (NCI)
Project Start
2006-09-01
Project End
2011-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
6
Fiscal Year
2006
Total Cost
$61,343
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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