Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control.
BRCA2 is a breast tumor suppressor with a potential function in the cellular response to DNA damage. BRCA2 binds to Rad51 through its BRC repeats. In support of the biological significance of this interaction, we found that the complex of BRCA2 and Rad51 in breast cancer MCF-7 cells was diminished upon conditional expression of a wild-type, but not a mutated, BRC4 repeat using the tetracycline-inducible system. Cells expressing a wild-type BRC4 repeat showed hypersensitivity to gamma-irradiation, an inability to form Rad51 radiation-induced foci, and a failure of radiation-induced G(2)/M, but not G(1)/S, checkpoint control. These results strongly suggest that the interaction between BRCA2 and Rad51 mediated by BRC repeats is critical for the cellular response to DNA damage.
Chen
C F
CF
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245, USA.
Chen
P L
PL
Zhong
Q
Q
Sharp
Z D
ZD
Lee
W H
WH
D000595:Amino Acid Sequence; D024682:BRCA2 Protein; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000528:radiation effects*; D002999:Clone Cells / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016195:G2 Phase; D005720:Gamma Rays; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D051135:Rad51 Recombinase; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016196:S Phase; D013752:Tetracycline / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D013752:Tetracycline