基因组不稳定性
DNA损伤
生物
DNA
DNA修复
癌症研究
DNA复制
癌症
癌基因
突变
衰老
细胞周期
细胞生物学
遗传学
基因
作者
Thanos D. Halazonetis,Vassilis G. Gorgoulis,Jiří Bártek
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2008-03-06
卷期号:319 (5868): 1352-1355
被引量:1739
标识
DOI:10.1126/science.1140735
摘要
Of all types of DNA damage, DNA double-strand breaks (DSBs) pose the greatest challenge to cells. One might have, therefore, anticipated that a sizable number of DNA DSBs would be incompatible with cell proliferation. Yet recent experimental findings suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs. This continuous formation of DNA DSBs may contribute to the genomic instability that characterizes the vast majority of human cancers. In addition, in precancerous lesions, these DNA DSBs activate p53 , which, by inducing apoptosis or senescence, raises a barrier to tumor progression. Breach of this barrier by various mechanisms, most notably by p53 mutations, that impair the DNA damage response pathway allows cancers to develop. Thus, oncogene-induced DNA damage may explain two key features of cancer: genomic instability and the high frequency of p53 mutations.
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