Donzelli Maddalena, Draetta Giulio F
European Institute of Oncology, 435 Via Ripamonti, 20141 Milan, Italy.
EMBO Rep. 2003 Jul;4(7):671-7. doi: 10.1038/sj.embor.embor887.
Precise monitoring of DNA replication and chromosome segregation ensures that there is accurate transmission of genetic information from a cell to its daughters. Eukaryotic cells have developed a complex network of checkpoint pathways that sense DNA lesions and defects in chromosome segregation, spindle assembly and the centrosome cycle, leading to an inhibition of cell-cycle progression for the time required to remove the defect and thus preventing genomic instability. The activation of checkpoints that are responsive to DNA damage or incomplete DNA replication ultimately results in the inhibition of cyclin-dependent kinases. This review focuses on our understanding of the biochemical mechanisms that specifically inactivate Cdc25 (cell division cycle 25) phosphatases to achieve this. The evidence for links between checkpoint deregulation and oncogenesis is discussed.
对DNA复制和染色体分离进行精确监测可确保遗传信息从一个细胞准确传递至其后代细胞。真核细胞已形成了一个复杂的检查点信号通路网络，该网络可感知DNA损伤以及染色体分离、纺锤体组装和中心体周期中的缺陷，从而在消除缺陷所需的时间内抑制细胞周期进程，进而防止基因组不稳定。对DNA损伤或DNA复制不完全作出反应的检查点激活最终会导致细胞周期蛋白依赖性激酶受到抑制。本综述着重于我们对特定使Cdc25（细胞分裂周期25）磷酸酶失活以实现此目的的生化机制的理解。文中还讨论了检查点失调与肿瘤发生之间联系的证据。
