The long-term objective of this proposal is to elucidate the relationship of a newly identified human gene, RAD51B, to breast cancer-related genes and therefore, breast cancer. Sequence homology suggests that RAD51B is functionally similar to HsRAD51 (human RAD51). The HsRAD51 gene product has recently been shown to interact with the p53, BRCA1, and BRCA2 proteins. Mutations disrupting the BRCA1 and BRCA2 tumor suppressor genes result in familial breast and ovarian cancer. In addition, p53 mutations have been found in familial breast cancer as well as in a large proportion of other cancers. These studies suggest a role for the HsRASD51 gene in breast tumorigenesis. Furthermore, recent discoveries indicate that RAD51B associates with HsRAD51 within a multi-protein complex by its interaction with another HsRAD51 homolog, RAD51C. In general, the RAD51 family of proteins function in pathways essential for genome stability, and given the HsRAD51-BRCA interactions, the study of the RAD51B gene and its function may be critical for the understanding of breast cancer etiology. The proposed project will explore the relationship of RAD51B to identified complex partners by further characterizing the RAD51B-RAD51C interaction. Additional studies will identify novel binding partners of RAD51B by testing for specific interactions of RAD51B with both BRCA1 and BRCA2. Several recent studies have attempted to characterize the interactions of breast cancer-related gene products using immunocytochemical techniques. HsRAD51 and BRCA1 have shown to co-localize in nuclear foci in a malignant breast cell line. The proposed project will further the understanding of the role of RAD51B in pathways involved in genome stability and recombination by examining RAD51B in these cellular structures both before and after insult by DNA damage. The relationship of RAD51B to identified protein partners will be examined by the localization of these proteins in normal and malignant breast cell lines and meiotic synaptonemal complexes. Recent studies have shown that RAD51B is damage inducible and cells deficient in RAD51B in normal and malignant breast cancer cell lines treated with these agents will be explored. These studies will help to identify protein factors interacting with RAD51B and thus provide insights into the biological role of the protein and its putative link to breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA081019-03
Application #
6513509
Study Section
Radiation Study Section (RAD)
Program Officer
Pelroy, Richard
Project Start
2000-06-01
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
3
Fiscal Year
2002
Total Cost
$293,692
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550