DNA double strand break repair and chromosomal translocation: Lessons from animal models
DNA double strand break repair and chromosomal translocation: Lessons from animal models
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DOI：
10.1038/sj.onc.1204767
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发表时间：
2001-09-10
期刊：
影响因子：
8
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Ferguson, DO;Alt, FW
维持基因组稳定性是对抗肿瘤转化的最重要的防御措施之一。尽管DNA双链自发断裂不断发生，但这一目标仍必须实现。这些危险的损伤可以通过双链断裂修复的两个主要途径来纠正；非同源末端连接和同源重组。最近使用小鼠模型的研究表明，任一途径的缺失都会导致基因组不稳定，包括潜在的致癌易位。由于易位涉及不同染色体的结合，因此必须存在细胞机制来在未修复的双链断裂的情况下创建这些结构。越来越多的证据表明，对生存如此重要的双链断裂修复途径本身可能就是产生潜在致命易位的罪魁祸首。讨论了双链断裂修复在预防和产生致癌核型变化中双重作用的证据和模型。
The maintenance of genomic stability is one of the most important defenses against neoplastic transformation. This objective must be accomplished despite a constant barrage of spontaneous DNA double strand breaks. These dangerous lesions are corrected by two primary pathways of double strand break repair; non homologous end joining and homologous recombination. Recent studies employing mouse models have shown that absence of either pathway leads to genomic instability, including potentially oncogenic translocations. Because translocations involve the union of different chromosomes, cellular machinery must exist that creates these structures in the context of unrepaired double strand breaks. Evidence is mounting that the pathways of double strand break repair that are so important for survival may themselves be the culprits that generate potentially fatal translocations. Evidence and models for the dual roles of double strand break repair in both preventing, and generating, oncogenic karyotypic changes are discussed.