Double-stranded DNA breaks activate a DNA damage checkpoint in G2 phase to trigger a cell cycle arrest, which can be reversed to allow for recovery. However, damaged G2 cells can also permanently exit the cell cycle, going into senescence or apoptosis, raising the question how an individual cell decides whether to recover or withdraw from the cell cycle. Here we find that the decision to withdraw from the cell cycle in G2 is critically dependent on the progression of DNA repair. We show that delayed processing of double strand breaks through HR-mediated repair results in high levels of resected DNA and enhanced ATR-dependent signalling, allowing p21 to rise to levels at which it drives cell cycle exit. These data imply that cells have the capacity to discriminate breaks that can be repaired from breaks that are difficult to repair at a time when repair is still ongoing.

中文翻译：

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持久的修复中间体会导致衰老。

双链DNA断裂激活了G2期的DNA损伤检查点，从而触发了细胞周期停滞，可以将其反转以恢复。但是，受损的G2细胞也可以永久退出细胞周期，进入衰老或凋亡状态，这引发了一个问题，即单个细胞如何决定是恢复还是退出细胞周期。在这里，我们发现退出G2细胞周期的决定主要取决于DNA修复的进程。我们显示通过HR介导的修复双链断裂的延迟处理导致高水平的切除的DNA和增强的ATR依赖性信号传导，使p21上升到其驱动细胞周期退出的水平。