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pmid 10551859
title 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.
authors
Chen CF
Chen PL
Zhong Q
Sharp ZD
Lee WH
journal J Biol Chem
year 1999
full_text_available false
doi 10.1074/jbc.274.46.32931

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.

Authors: Chen CF, Chen PL, Zhong Q, Sharp ZD, Lee WH Journal: J Biol Chem (1999) DOI: 10.1074/jbc.274.46.32931

Abstract

  1. J Biol Chem. 1999 Nov 12;274(46):32931-5. doi: 10.1074/jbc.274.46.32931.

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.

Chen CF(1), Chen PL, Zhong Q, Sharp ZD, Lee WH.

Author information: (1)Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center, San Antonio, Texas 78245, USA.

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.

DOI: 10.1074/jbc.274.46.32931 PMID: 10551859 [Indexed for MEDLINE]