DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1 checkpoint control is common in cancer through TP53, ATM mutations, Rb loss or cyclin E overexpression, providing a stronger rationale for targeting the S/G2 checkpoints. This review will focus on the ATM-CHK2-p53-p21 pathway and the ATR-CHK1-WEE1 pathway and ongoing efforts to target these pathways for patient benefit.

中文翻译：

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癌症中的 DNA 损伤检查点激酶

DNA 损伤反应 (DDR) 通路可防止高水平的内源性和环境 DNA 损伤通过细胞周期检查点信号和 DNA 修复通路的协调和集成网络复制并传递给下一代细胞。根据损伤的类型，以及它在细胞周期中发生的位置，涉及不同的通路，ATM-CHK2-p53 通路控制 G1 检查点或 ATR-CHK1-Wee1 通路控制 S 和 G2/M 检查点。G1检查点控制的丧失在癌症中很常见TP53，自动柜员机突变、Rb 丢失或细胞周期蛋白 E 过度表达，为靶向 S/G2 检查点提供了更强有力的理由。本综述将重点关注 ATM-CHK2-p53-p21 通路和 ATR-CHK1-WEE1 通路以及针对这些通路的持续努力，以使患者受益。