Expression of BRC repeats in breast cancer cells disrupts the BRCA2- Rad51 complex and leads to radiation hypersensitivity and loss of G2/M checkpoint control

Chi Fen Chen, Phang Lang Chen, Qing Zhong, Zelton D Sharp, Wen Hwa Lee

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

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 γ-irradiation, an inability to form Rad51 radiation-induced foci, and a failure of radiation-induced G2/M, but not G1/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.

Original languageEnglish (US)
Pages (from-to)32931-32935
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number46
DOIs
StatePublished - Nov 12 1999

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DNA Damage
Hypersensitivity
Cells
Radiation
Breast Neoplasms
DNA
MCF-7 Cells
Tetracycline
Tumors
Irradiation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression of BRC repeats in breast cancer cells disrupts the BRCA2- Rad51 complex and leads to radiation hypersensitivity and loss of G2/M checkpoint control. / Chen, Chi Fen; Chen, Phang Lang; Zhong, Qing; Sharp, Zelton D; Lee, Wen Hwa.

In: Journal of Biological Chemistry, Vol. 274, No. 46, 12.11.1999, p. 32931-32935.

Research output: Contribution to journalArticle

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abstract = "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 γ-irradiation, an inability to form Rad51 radiation-induced foci, and a failure of radiation-induced G2/M, but not G1/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.",
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