p53 deficiency does not affect the accumulation of point mutations in a transgene target.
p53 deficiency does not affect the accumulation of point mutations in a transgene target.
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p53 缺陷不会影响转基因靶标中点突变的积累。
DOI：
10.1073/pnas.92.18.8517
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发表时间：
1995
影响因子：
11.1
通讯作者：
Bradley,A
中科院分区：
文献类型：
--
作者：
Sands,AT;Suraokar,MB;Sanchez,A;Marth,JE;Donehower,LA;Bradley,A
生物体需要DNA修复来防止突变的积累并保持遗传信息的完整性。已经用损伤DNA的试剂处理的哺乳动物细胞具有p53水平的增加、细胞周期中G1期的p53依赖性停滞和p53依赖性凋亡应答。据推测，这种细胞周期进程的阻滞是必要的，以便有时间进行DNA修复或将受损细胞引导至凋亡途径。这一假说预测，p53缺陷细胞将有一个异常的凋亡反应，并表现出“突变”表型。使用一个敏感的点突变，小缺失和插入的积累试验，我们直接测试是否p53缺陷细胞表现出增加的突变频率之前和之后暴露于DNA损伤剂。我们报告说，野生型和p53缺陷的成纤维细胞，胸腺细胞和肿瘤组织中的转基因lacI靶基因的点突变积累率难以区分。这些结果表明，p53在G1检查点控制和肿瘤抑制中的作用不影响点突变的积累。
DNA repair is required by organisms to prevent the accumulation of mutations and to maintain the integrity of genetic information. Mammalian cells that have been treated with agents that damage DNA have an increase in p53 levels, a p53-dependent arrest at G1 in the cell cycle, and a p53-dependent apoptotic response. It has been hypothesized that this block in cell cycle progression is necessary to allow time for DNA repair or to direct the damaged cell to an apoptotic pathway. This hypothesis predicts that p53-deficient cells would have an abnormal apoptotic response and exhibit a "mutator" phenotype. Using a sensitive assay for the accumulation of point mutations, small deletions, and insertions, we have directly tested whether p53-deficient cells exhibit an increased frequency of mutation before and after exposure to DNA-damaging agents. We report that wild-type and p53-deficient fibroblasts, thymocytes, and tumor tissue have indistinguishable rates of point mutation accumulation in a transgenic lacI target gene. These results suggest that the role of p53 in G1 checkpoint control and tumor suppression does not affect the accumulation of point mutations.