p53 directly enhances rejoining of DNA double-strand breaks with cohesive ends in gamma-irradiated mouse fibroblasts.
p53 directly enhances rejoining of DNA double-strand breaks with cohesive ends in gamma-irradiated mouse fibroblasts.
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DOI：
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发表时间：
1999-06
期刊：
影响因子：
11.2
通讯作者：
W. Tang;H. Willers;S. Powell
中科院分区：
文献类型：
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作者：
W. Tang;H. Willers;S. Powell
p53基因调节细胞周期对DNA损伤的反应，这可能为足够的DNA修复提供时间。我们问是否p53可以直接增加修复定义的双链断裂（DSB）的非同源末端连接在γ射线照射的小鼠胚胎成纤维细胞与不同的p53状态。通过使用附加型质粒再激活试验，我们发现野生型p53的存在增强了单链DNA短互补末端的DSB的再连接。p53似乎直接参与了这种调节，因为重新连接增强依赖于COOH末端结构域介导的非特异性DNA结合活性的存在，并且独立于反式激活功能。我们假设缺乏p53的肿瘤细胞和具有野生型p53的正常细胞可能使用不同的途径来修复辐射诱导的DSB。
The p53 gene regulates the cell cycle response to DNA damage, which may allow time for adequate DNA repair. We asked whether p53 could directly increase the repair of defined double-strand breaks (DSBs) by nonhomologous end-joining in gamma-irradiated mouse embryonic fibroblasts with differing p53 status. By using an episomal plasmid reactivation assay, we found that presence of wild-type p53 enhanced rejoining of DSBs with short complementary ends of single-stranded DNA. p53 appeared to be directly involved in this regulation, because rejoining enhancement was dependent on the presence of nonspecific DNA binding activity as mediated by the COOH-terminal domain and was independent of transactivating function. We hypothesize that tumor cells lacking p53 and normal cells with wild-type p53 may use different pathways for repair of radiation-induced DSBs.