An Oncogene-Induced DNA Damage Model for Cancer Development Export

@article{citeulike:2480760, abstract = {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. 10.1126/science.1140735}, author = {Halazonetis, Thanos D. and Gorgoulis, Vassilis G. and Bartek, Jiri}, citeulike-article-id = {2480760}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1140735}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/319/5868/1352}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18323444}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18323444}, day = {7}, doi = {10.1126/science.1140735}, journal = {Science}, keywords = {damage, dna, oncogene}, month = {March}, number = {5868}, pages = {1352--1355}, posted-at = {2008-04-11 04:22:19}, priority = {3}, title = {An Oncogene-Induced DNA Damage Model for Cancer Development}, url = {http://dx.doi.org/10.1126/science.1140735}, volume = {319}, year = {2008} }

TY - JOUR ID - citeulike:2480760 L3 - citeulike-article-id:2480760 N2 - 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. 10.1126/science.1140735 IS - 5868 JF - Science EP - 1355 TI - An Oncogene-Induced DNA Damage Model for Cancer Development VL - 319 SP - 1352 KW - damage KW - dna KW - oncogene AU - Halazonetis, Thanos AU - Gorgoulis, Vassilis AU - Bartek, Jiri PY - 2008/03/07/ UR - http://dx.doi.org/10.1126/science.1140735 ER -