BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 15; pp. 3547 - 3551
• Main Authors: YUAN, S.-S. F, LEE, S.-Y, GANG CHEN, MEIHUA SONG, TOMLINSON, G. E, LEE, E. Y.-H. P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.1999
• Subjects: Animals; Biological and medical sciences; BRCA1 Protein - deficiency; BRCA1 Protein - genetics; BRCA2 Protein; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cisplatin - pharmacology; COS Cells; DNA Damage; DNA Repair - drug effects; DNA Repair - genetics; DNA-Binding Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Genes, BRCA1; Humans; Macromolecular Substances; Molecular and cellular biology; Neoplasm Proteins - deficiency; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Rad51 Recombinase; Recombinant Fusion Proteins - biosynthesis; Recombination, Genetic - drug effects; Recombination, Genetic - genetics; Recombination, Genetic - radiation effects; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; Human; Ionizing irradiation; Gene product; Established cell line; Mutation; Gene expression; Mechanism of action; Fusion protein; In vitro; Tumor cell; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

Mutations in BRCA1 and BRCA2 account for the majority of familial breast cancers. Cells with mutated BRCA1 or BRCA2 are hypersensitive to ionizing radiation (IR) and exhibit defective DNA repair. Both BRCA1 and BRCA2 have been reported to bind Rad51, a protein essential for homologous recombination and the recombinational repair of DNA double-strand breaks. In normal cells, a redistribution of Rad51 protein, manifested as formation of Rad51 nuclear foci, is seen upon IR treatment. Here we demonstrate that IR-induced Rad51 foci formation is aberrant in BRCA2- but not BRCA1-deficient tumor cells. In Capan-1 cells, which do not express functional BRCA2, there was little Rad51 foci formation in response to a wide range of radiation dosages. Moreover, forced expression of a fusion protein containing green fluorescent protein and the first Rad51-binding BRC repeat of BRCA2 in cells with wild-type BRCA2 rendered them hypersensitive to IR and cisplatin and compromised IR-induced Rad51 foci formation. In HCC1937 cells, which harbor mutation of BRCA1, IR-induced Rad51 foci were readily detected. This study suggests a requirement of BRCA2 protein for the IR-induced assembly of Rad51 complex in vivo.