Understanding the limitations of radiation-induced cell cycle checkpoints.
Understanding the limitations of radiation-induced cell cycle checkpoints.
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DOI：
10.3109/10409238.2011.575764
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发表时间：
2011-08
影响因子：
6.5
通讯作者：
Löbrich M
中科院分区：
文献类型：
--
作者：
Deckbar D;Jeggo PA;Löbrich M
DNA损伤反应通路涉及双链断裂修复和细胞周期检查点控制过程，以防止或限制进入S期或在存在未修复损伤的情况下进行有丝分裂。检查点可以永久地将受损细胞从活跃的增殖群体中移除，但也可以暂时停止细胞周期，为DSB的修复提供时间。虽然检查点在限制基因组不稳定性方面是有效的，但它并不是万无一失的，但存在固有的局限性。最近的工作表明，G1/S检查点被缓慢激活，并允许细胞在未修复的DSB存在下，在照射后约4-6小时进入S期。在此期间，只观察到S阶段的进入是缓慢的，但不是取消的。相比之下，G2/M检查点被快速激活，但仅响应10-20个DSB的水平，因此DSB数量较少的细胞在修复完成之前不会启动检查点或终止停止。在这里，我们在目前对所涉因素的了解的背景下讨论这些检查站的局限性。我们认为，完全激活G1/S阻滞所需的时间反映了G1期进程中存在一个限制点。这一点以前被定义为有丝分裂原饥饿无法阻止细胞进入S期的点。然而，通过限制点的细胞可以对DSB做出反应，尽管效率降低。
The DNA damage response pathways involve processes of double-strand break (DSB) repair and cell cycle checkpoint control to prevent or limit entry into S phase or mitosis in the presence of unrepaired damage. Checkpoints can function to permanently remove damaged cells from the actively proliferating population but can also halt the cell cycle temporarily to provide time for the repair of DSBs. Although efficient in their ability to limit genomic instability, checkpoints are not foolproof but carry inherent limitations. Recent work has demonstrated that the G1/S checkpoint is slowly activated and allows cells to enter S phase in the presence of unrepaired DSBs for about 4–6 h post irradiation. During this time, only a slowing but not abolition of S-phase entry is observed. The G2/M checkpoint, in contrast, is quickly activated but only responds to a level of 10–20 DSBs such that cells with a low number of DSBs do not initiate the checkpoint or terminate arrest before repair is complete. Here, we discuss the limitations of these checkpoints in the context of the current knowledge of the factors involved. We suggest that the time needed to fully activate G1/S arrest reflects the existence of a restriction point in G1-phase progression. This point has previously been defined as the point when mitogen starvation fails to prevent cells from entering S phase. However, cells that passed the restriction point can respond to DSBs, albeit with reduced efficiency.
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影响因子：
64.5
作者：
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作者：
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通讯作者：
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