Open AccessThe BRCA 2 gene product functionally interacts with p53 and RAD51
Author(s) -
Lihua Y. Marmorstein,
Toru Ouchi,
Stuart A. Aaronson
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.23.13869
Subject(s) - rad51 , biology , brca2 protein , dna repair , dna damage , gene , cancer research , microbiology and biotechnology , gene product , transcriptional regulation , mutation , genetics , dna , germline mutation , gene expression
Germ-line mutations in the humanBRCA2 gene confer susceptibility to breast cancer. Efforts to elucidate its function have revealed a putative transcriptional activation domain andin 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 theBRCA2 gene product is a 460-kDa nuclear phosphoprotein, which formsin 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.