Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage.
Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage.
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发表时间：
1993-09
期刊：
影响因子：
11.2
通讯作者：
W. Slichenmyer;W. Nelson;R. Slebos;M. Kastan
中科院分区：
文献类型：
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作者：
W. Slichenmyer;W. Nelson;R. Slebos;M. Kastan
细胞周期检查点通过细胞周期调节进程。在酵母中，由于rad9基因突变导致G2检查点丢失，导致遗传不稳定性增加以及对电离辐射的敏感性增加。相比之下，除了p53功能状态外，比较同基因细胞的克隆存活率，我们发现哺乳动物细胞中G1检查点的丢失与电离辐射或拓扑异构酶I抑制剂喜树碱的致死效应的敏感性增加无关。这些结果表明，对DNA损伤剂的敏感性增加不一定是哺乳动物细胞周期检查点的定义特征。此外，在最近的链接的p53功能辐射诱导的造血细胞凋亡，这些观察表明，p53依赖性细胞凋亡是一种细胞类型特异性的现象，从而预测的生物学后果的损失p53功能将是细胞类型特异性。
Cell cycle checkpoints regulate progression through the cell cycle. In yeast, loss of the G2 checkpoint by mutation of the rad9 gene results in increased genetic instability as well as increased sensitivity to ionizing radiation. In contrast, comparing clonogenic survival of cells which are isogeneic except for p53 functional status, we find that loss of a G1 checkpoint in mammalian cells is not associated with increased sensitivity to the lethal effects of ionizing radiation or a topoisomerase I inhibitor, camptothecin. These results indicate that increased sensitivity to DNA-damaging agents is not necessarily a defining feature of a mammalian cell cycle checkpoint. Furthermore, in light of a recent link of p53 function to radiation-induced apoptosis in hematopoietic cells, these observations suggest that p53-dependent apoptosis is a cell type-specific phenomenon and thus predict that the biological consequences of loss of p53 function will be cell type specific.