Cell cycle events are coordinated by cyclin-dependent kinases (CDKs) to ensure robust cell division. CDK4/6 and CDK2 regulate the growth 1 (G 1 ) to synthesis (S) phase transition of the cell cycle by responding to mitogen signaling, promoting E2F transcription and inhibition of the anaphase-promoting complex. We found that this mechanism was still required in G 2 -arrested cells to prevent cell cycle exit after the S phase. This mechanism revealed a role for CDK4/6 in maintaining the G 2 state, challenging the notion that the cell cycle is irreversible and that cells do not require mitogens after passing the restriction point. Exit from G 2 occurred during ribotoxic stress and was actively mediated by stress-activated protein kinases. Upon relief of stress, a significant fraction of cells underwent a second round of DNA replication that led to whole-genome doubling.

中文翻译：

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G 2 停滞期间需要 CDK4/6 活性，以防止应激诱导的内复制

细胞周期事件由细胞周期蛋白依赖性激酶 (CDK) 协调，以确保稳健的细胞分裂。 CDK4/6 和 CDK2 调节生长 1 (G1）通过响应有丝分裂原信号、促进 E2F 转录和抑制后期促进复合物，向细胞周期的合成 (S) 相转变。我们发现G中仍然需要这个机制2- 抑制细胞以防止细胞周期在 S 期后退出。该机制揭示了 CDK4/6 在维持 G 中的作用2状态，挑战细胞周期不可逆以及细胞在通过限制点后不需要有丝分裂原的观念。从G退出2发生在核糖毒性应激期间，并由应激激活的蛋白激酶主动介导。压力缓解后，很大一部分细胞经历了第二轮 DNA 复制，导致全基因组加倍。