Related Experiment Videos
The BRCA2 gene product functionally interacts with p53 and RAD51
L Y Marmorstein1, T Ouchi, S A Aaronson
1The Derald H. Ruttenberg Cancer Center, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029, USA.
Abstract:
Germ-line mutations in the human BRCA2 gene confer susceptibility to breast cancer. Efforts to elucidate its function have revealed a putative transcriptional activation domain and in vitro interaction with the DNA repair protein RAD51. Other studies have indicated that RAD51 physically associates with the p53 tumor suppressor protein. Here we show that the BRCA2 gene product is a 460-kDa nuclear phosphoprotein, which forms in vivo complexes with both p53 and RAD51. Moreover, exogenous BRCA2 expression in cancer cells inhibits p53's transcriptional activity, and RAD51 coexpression enhances BRCA2's inhibitory effects. These findings demonstrate that BRCA2 physically and functionally interacts with two key components of cell cycle control and DNA repair pathways. Thus, BRCA2 likely participates with p53 and RAD51 in maintaining genome integrity.
Insights
Germ-line mutations in the BRCA2 gene increase breast cancer risk. BRCA2 interacts with RAD51 and p53 proteins, suggesting a role in maintaining genome integrity and DNA repair.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Germ-line mutations in the human BRCA2 gene are linked to breast cancer susceptibility.
- BRCA2 has a putative transcriptional activation domain and interacts with RAD51 in vitro.
- RAD51 is known to associate with the p53 tumor suppressor protein.
Purpose of the Study:
- To investigate the in vivo interactions and functional relationship of the BRCA2 gene product with p53 and RAD51.
- To determine if BRCA2 participates in cell cycle control and DNA repair pathways.
Main Methods:
- Characterization of the BRCA2 gene product as a nuclear phosphoprotein.
- Analysis of in vivo complex formation between BRCA2, p53, and RAD51.
- Assessment of the effects of exogenous BRCA2 and RAD51 expression on p53's transcriptional activity in cancer cells.
Main Results:
- The BRCA2 gene product is identified as a 460-kDa nuclear phosphoprotein.
- BRCA2 forms in vivo complexes with both p53 and RAD51.
- BRCA2 expression inhibits p53's transcriptional activity, an effect enhanced by RAD51 coexpression.
Conclusions:
- BRCA2 physically and functionally interacts with p53 and RAD51.
- These interactions suggest BRCA2 plays a role in cell cycle control and DNA repair.
- BRCA2, p53, and RAD51 likely collaborate to maintain genome integrity.