Bertrand Pascale, Saintigny Yannick, Lopez Bernard S
UMR CEA/CNRS 217, CEA, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 18 route du panorama, 92265, Fontenay-aux-Roses, Cedex, France.
Trends Genet. 2004 Jun;20(6):235-43. doi: 10.1016/j.tig.2004.04.003.
The tumor suppressor protein p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes. However, data from various laboratories suggest an additional role for p53: transcription-independent suppression of homologous recombination (HR). Genetic and physical interactions among p53, HR proteins (e.g. RAD51 and RAD54) and HR-DNA intermediates show that p53 acts directly on HR during the early and late steps of recombination. Complementary to the MSH2 mismatch-repair system, p53 appears to impair excess HR by controlling the minimal efficiency processing segment and by reversing recombination intermediates. By controlling the balance between the BLM and the RAD51 pathways, this direct role of p53 could maintain genome stability when replication forks are stalled at regions of DNA damage. In this article, we discuss the direct role of p53 on HR and the consequences for genome stability, tumor protection and speciation.
肿瘤抑制蛋白p53通过激活多个基因的转录来控制细胞周期检查点和细胞凋亡。然而，来自不同实验室的数据表明p53还有另外一个作用：对同源重组（HR）的转录非依赖性抑制。p53、HR蛋白（如RAD51和RAD54）以及HR-DNA中间体之间的遗传和物理相互作用表明，p53在重组的早期和晚期步骤中直接作用于HR。与MSH2错配修复系统互补，p53似乎通过控制最小效率加工片段和逆转重组中间体来损害过量的HR。通过控制BLM和RAD51途径之间的平衡，当复制叉在DNA损伤区域停滞时，p53的这种直接作用可以维持基因组稳定性。在本文中，我们讨论了p53对HR的直接作用以及对基因组稳定性、肿瘤保护和物种形成的影响。
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