Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-5671, USA.
FEBS J. 2010 Aug;277(15):3079-85. doi: 10.1111/j.1742-4658.2010.07734.x. Epub 2010 Jul 1.
The tumor suppressor, breast cancer susceptibility gene 1 (BRCA1), plays an integral role in the maintenance of genome stability and, in particular, the cellular response to DNA damage. Here, the emerging role of BRCA1 in nonhomologous end-joining-mediated DNA repair following DNA damage will be reviewed, as well as the activation of apoptotic pathways. The control of these functions via DNA damage-induced BRCA1 shuttling will also be discussed, in particular BRCA1 shuttling induced by erlotinib and irradiation. Finally, the potential targeting of BRCA1 shuttling as a novel strategy to sensitize cells to DNA damage will be entertained.
抑癌基因、乳腺癌易感基因 1（BRCA1）在维持基因组稳定性方面发挥着重要作用，特别是在细胞对 DNA 损伤的反应中。在此，将综述 BRCA1 在 DNA 损伤后非同源末端连接介导的 DNA 修复以及凋亡途径的激活中的新兴作用。还将讨论通过 DNA 损伤诱导的 BRCA1 穿梭来控制这些功能，特别是 ER 阳性乳腺癌中表皮生长因子受体抑制剂（erlotinib）和放疗诱导的 BRCA1 穿梭。最后，将探讨将 BRCA1 穿梭作为一种使细胞对 DNA 损伤敏感的新策略的潜在靶点。
