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
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
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DOI：
10.1074/jbc.274.46.32931
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发表时间：
1999-11-12
影响因子：
4.8
通讯作者：
Lee, WH
中科院分区：
文献类型：
--
作者：
Chen, CF;Chen, PL;Lee, WH
BRCA2是一种乳腺肿瘤抑制因子，在细胞对DNA损伤的反应中具有潜在的功能。BRCA2通过BRC重复序列与Rad51结合。为了支持这种相互作用的生物学意义，我们发现乳腺癌MCF-7细胞中的BRCA2和Rad51复合物在使用四环素诱导系统的野生型条件表达时减少，而不是突变的BRC4重复。表达野生型BRC4重复序列的细胞表现出对γ辐照的超敏反应，无法形成Rad51辐射诱导的病灶，以及辐射诱导的G(2)/M失败，但G(I)/S没有。这些结果强烈表明BRC重复序列介导的BRCA2和Rad51之间的相互作用对于细胞对DNA损伤的反应至关重要。
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(I)/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.