Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100006, China.
National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing ,100088, China.
Int J Med Sci. 2017 Sep 30;14(12):1292-1300. doi: 10.7150/ijms.21510. eCollection 2017.
The immediate early response gene 5 (5) is a radiation response gene induced in a dose-independent manner, and has been suggested to be a molecular biomarker for biodosimetry purposes upon radiation exposure. Here, we investigated the function of IER5 in DNA damage response and repair. We found that interference on IER5 expression significantly decreased the efficiency of repair of DNA double-strand breaks induced by ionizing radiations in Hela cells. We found that IER5 participates in the non-homologous end-joining pathway of DNA breaks repair. Additionally, we identified a number of potential IER5-interacting proteins through mass spectrometry-based protein assays. The interaction of IER5 protein with poly(ADP-Ribose) polymerase 1 (PARP1) and Ku70 was further confirmed by immunoprecipitation assays. We also found that Olaparib, a PARP1 inhibitor, affected the stability of IER5. These results indicate that targeting of IER5 may be a novel DNA damage response-related strategy to use during cervical cancer radiotherapy or chemotherapy.
立即早期反应基因 5(IER5)是一种非剂量依赖性诱导的辐射反应基因,被认为是辐射暴露后用于生物剂量测定的分子生物标志物。在这里,我们研究了 IER5 在 DNA 损伤反应和修复中的功能。我们发现,IER5 表达的干扰显著降低了 HeLa 细胞中电离辐射诱导的 DNA 双链断裂修复的效率。我们发现 IER5 参与了 DNA 断裂修复的非同源末端连接途径。此外,我们通过基于质谱的蛋白质分析鉴定了一些潜在的 IER5 相互作用蛋白。免疫沉淀实验进一步证实了 IER5 蛋白与聚(ADP-核糖)聚合酶 1(PARP1)和 Ku70 的相互作用。我们还发现,PARP1 抑制剂奥拉帕尼(Olaparib)影响 IER5 的稳定性。这些结果表明,靶向 IER5 可能是一种新的与宫颈癌放化疗相关的 DNA 损伤反应策略。