Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G(1) arrest
Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G(1) arrest
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DOI：
10.1073/pnas.93.10.4827
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发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Wahl, GM
中科院分区：
文献类型：
--
作者：
Huang, LC;Clarkin, KC;Wahl, GM
肿瘤抑制因子p53通过诱导细胞周期停滞或细胞凋亡来维持基因组稳定性，以响应产生DNA损伤的条件。线性化质粒DNA、具有大缺口的环状DNA或单链环状噬菌粒的核注射足以诱导p53依赖性停滞。超螺旋和带切口的质粒DNA以及具有小间隙的环状DNA是无效的。滴定实验表明，正常人成纤维细胞中的阻滞机制可以通过非常少的双链断裂来激活，并且仅一个双链断裂可能就足够了。聚合酶链反应分析表明，在血清阻滞的人成纤维细胞中，末端连接活性较低，当细胞通过G（1）期或进入S期时，连接活性较高。我们认为p53依赖的G（1）阻滞的高度敏感性部分是由于G（1）早期某些类型的DNA损伤修复效率低下。
The tumor suppressor p53 contributes to maintaining genome stability by inducing a cell cycle arrest or apoptosis in response to conditions that generate DNA damage. Nuclear injection of linearized plasmid DNA, circular DNA with a large gap, or single-stranded circular phagemid is sufficient to induce a p53-dependent arrest. Supercoiled and nicked plasmid DNA, and circular DNA with a small gap were ineffective, Titration experiments indicate that the arrest mechanism in normal human fibroblasts can be activated by very few double strand breaks, and only one may be sufficient. Polymerase chain reaction assays showed that end-joining activity is low in serum-arrested human fibroblasts, and that higher joining activity occurs as cells proceed through G(1) or into S phase. We propose that the exquisite sensitivity of the p53-dependent G(1) arrest is partly due to inefficient repair of certain types of DNA damage in early G(1).