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- Thanos D. Halazonetis
- Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland.
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- Vassilis G. Gorgoulis
- Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland.
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- Jiri Bartek
- Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland.
書誌事項
- 公開日
- 2008-03-07
- DOI
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- 10.1126/science.1140735
- 公開者
- American Association for the Advancement of Science (AAAS)
この論文をさがす
説明
<jats:p> 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 <jats:italic>p53</jats:italic> , which, by inducing apoptosis or senescence, raises a barrier to tumor progression. Breach of this barrier by various mechanisms, most notably by <jats:italic>p53</jats:italic> 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 <jats:italic>p53</jats:italic> mutations. </jats:p>
収録刊行物
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- Science
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Science 319 (5868), 1352-1355, 2008-03-07
American Association for the Advancement of Science (AAAS)
