The BRCA2 gene product functionally interacts with p53 and RAD51.
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.
Marmorstein
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The Derald H. Ruttenberg Cancer Center, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029, USA.
Ouchi
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Aaronson
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D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D018095:Germ-Line Mutation; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D051135:Rad51 Recombinase; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C495153:RAD51 protein, human; D051135:Rad51 Recombinase