PMID- 10551859 OWN - NLM STAT- MEDLINE DCOM- 20000103 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 46 DP - 1999 Nov 12 TI - 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. PG - 32931-5 AB - 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. FAU - Chen, C F AU - Chen CF AD - Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245, USA. FAU - Chen, P L AU - Chen PL FAU - Zhong, Q AU - Zhong Q FAU - Sharp, Z D AU - Sharp ZD FAU - Lee, W H AU - Lee WH LA - eng GR - CA30195/CA/NCI NIH HHS/United States GR - CA58183/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (BRCA2 Protein) RN - 0 (DNA-Binding Proteins) RN - 0 (Luminescent Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Transcription Factors) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.7.- (RAD51 protein, human) RN - EC 2.7.7.- (Rad51 Recombinase) RN - F8VB5M810T (Tetracycline) SB - IM MH - Amino Acid Sequence MH - BRCA2 Protein MH - Breast Neoplasms MH - Cell Cycle/*radiation effects MH - Clone Cells/radiation effects MH - DNA Damage/genetics MH - DNA-Binding Proteins/*genetics/metabolism MH - G2 Phase MH - Gamma Rays MH - Green Fluorescent Proteins MH - Humans MH - Luminescent Proteins MH - Microscopy, Fluorescence MH - Mitosis MH - Molecular Sequence Data MH - Mutation MH - Neoplasm Proteins/*genetics/metabolism MH - Protein Binding MH - Rad51 Recombinase MH - Repetitive Sequences, Nucleic Acid/genetics MH - S Phase MH - Tetracycline/pharmacology MH - Transcription Factors/*genetics/metabolism MH - Tumor Cells, Cultured EDAT- 1999/11/07 00:00 MHDA- 1999/11/07 00:01 CRDT- 1999/11/07 00:00 PHST- 1999/11/07 00:00 [pubmed] PHST- 1999/11/07 00:01 [medline] PHST- 1999/11/07 00:00 [entrez] AID - S0021-9258(17)46598-7 [pii] AID - 10.1074/jbc.274.46.32931 [doi] PST - ppublish SO - J Biol Chem. 1999 Nov 12;274(46):32931-5. doi: 10.1074/jbc.274.46.32931.