Although cyclin G1 has been implicated in certain p53-related biological phenomena, other aspects of its function remain unclear. Here we report hitherto unknown mechanism by which cyclin G1 increases radiation sensitivity by regulating the level of cyclin B1. Overexpression of cyclin G1 was observable in lung carcinoma tissues. Irradiation of human lung cells with cyclin G1 overexpression resulted in increased cell death and gamma-H2AX foci suggesting that cyclin G1 rendered the cells more susceptible to DNA damage. Enhanced radiosensitivity by cyclin G1 was correlated with increased cyclin B1, CDC2/cyclin B1 complex, and MPM2. Cell cycle synchronization clearly showed coexpression of cyclin G1 and cyclin B1 in G2/M phase. Depletion of cyclin G1 by interference RNA revealed that cyclin G1 regulated transcription of cyclin B1 in a p53-independent manner, and confirmed that the increased mitotic cells and cell death by cyclin G1 were dependent upon cyclin B1. Therefore, our data suggest that cyclin G1 enhanced radiation sensitivity by overriding radiation-induced G2 arrest through transcriptional upregulation of cyclin B1.

中文翻译：

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细胞周期蛋白G1克服了辐射诱导的G2阻滞，并通过细胞周期蛋白B1的转录激活增加了细胞死亡。

尽管细胞周期蛋白G1与某些与p53相关的生物学现象有关，但其功能的其他方面仍不清楚。在这里我们报告迄今未知的机制，细胞周期蛋白G1通过调节细胞周期蛋白B1的水平来增加辐射敏感性。在肺癌组织中观察到细胞周期蛋白G1的过表达。细胞周期蛋白G1过表达对人肺细胞的照射导致细胞死亡和伽马H2AX灶增加，这表明细胞周期蛋白G1使细胞更容易受到DNA损伤。细胞周期蛋白G1增强的放射敏感性与细胞周期蛋白B1，CDC2 /细胞周期蛋白B1复合体和MPM2的增加有关。细胞周期同步清楚地表明细胞周期蛋白G1和细胞周期蛋白B1在G2 / M期共表达。干扰RNA对细胞周期蛋白G1的消耗表明，细胞周期蛋白G1以p53独立的方式调节细胞周期蛋白B1的转录，并证实细胞周期蛋白G1增加的有丝分裂细胞和细胞死亡均依赖于细胞周期蛋白B1。因此，我们的数据表明细胞周期蛋白G1通过覆盖细胞周期蛋白B1的转录上调来替代辐射诱导的G2阻滞，从而增强了辐射敏感性。