Levy Antonin, Albiges-Sauvin Laurence, Massard Christophe, Soria Jean-Charles, Deutsch Eric
Institut Gustave-Roussy, service de radiothérapie oncologie, université Paris-XI, Villejuif, France.
Bull Cancer. 2011 Oct;98(9):1037-45. doi: 10.1684/bdc.2011.1382.
Genomic DNA is constantly under stress of endogenous and exogenous DNA damaging agents. Without proper care, the DNA damage causes an alteration of the genomic structure and can lead to cell death or the occurrence of mutations involved in tumorigenesis. During the process of evolution, organisms have acquired a series of response mechanisms and repair of DNA damage, thereby ensuring the maintenance of genome stability and faithful transmission of genetic information. The checkpoints are the major mechanisms by which a cell can respond to DNA damage, either by actively stopping the cell cycle or by induction of apoptosis. Two parallel signalling pathways, ATM and ATR respond to genotoxic stress by activating their downstream target proteins including the two effectors kinases CHK1 and CHK2. Promising preliminary data render these proteins potential targets for therapeutic development against cancer.
基因组DNA不断受到内源性和外源性DNA损伤剂的压力。如果没有适当的保护,DNA损伤会导致基因组结构改变,并可能导致细胞死亡或发生与肿瘤发生相关的突变。在进化过程中,生物体获得了一系列DNA损伤的反应机制和修复机制,从而确保基因组稳定性的维持和遗传信息的准确传递。检查点是细胞对DNA损伤作出反应的主要机制,要么通过主动停止细胞周期,要么通过诱导细胞凋亡。两条平行的信号通路,ATM和ATR通过激活其下游靶蛋白(包括两个效应激酶CHK1和CHK2)来响应基因毒性应激。有前景的初步数据使这些蛋白成为抗癌治疗开发的潜在靶点。