中文摘要：

肿瘤的发生与癌基因的激活或抑癌基因的失活有着密不可分的关系.癌基因的活化及抑癌基因的抑制可引发细胞内染色体基因组的复制应激反应.持续的复制应激反应可导致双链DNA断裂或单链DNA复制中间体的产生,从而分别激活两个重要的DNA损伤反应（DDR）通路,即ATM和ATR通路.与此同时,DDR检查点在感知DNA损伤信号后,可诱发细胞周期阻滞.只有损伤的DNA在得以正确修复以后,细胞周期才能再次启动.在细胞发生肿瘤转化的情况下,癌基因在引发DNA损伤的同时,常通过多种途径抑制DDR反应,导致染色体异常的重组与分离,进而促进肿瘤的生成;而癌基因造成的持续的损伤反应,未通过DDR检验点,还可引发细胞的另外一种结局,即最终细胞的老化死亡.

英文摘要：

Tumorigenesis is closely related to the activation of oncogene or inactivation of tumor suppressor gene. The activation of oncogene or suppression of tumor suppressor gene can induce the replication stress of human chromosome genome. The sustained reaction of replication stress often results in the accumulation of double strand break or single strand DNA replication intermediate, which will in turn activate two important DNA damage response （DDR） pathways, ATM and ATR pathway, respectively. Mean- while, the detection of the damaged signal by DDR check point can induce cell cycle arrest. Only upon the correct repair on these damage DNAs, the cell cycle can re-initiate. In the presence of cellular transformation, oncogene not only induces DNA damage, but also promotes tumorigenesis by inhibiting DDR through multiple pathways that may eventually lead to the aberrant recombination and/or segregation of the replicative chromosomes. In addition, the sustained DDR induced by oncogene fails to pass the DDR checkpoint which will lead to another cellular outcome, the final cell death through senescence.