English: ATM-mediated two-step response to DNA double strand breaks. In the rapid response activated ATM phosphorylates effector kinase CHK2 which phosphorylates CDC25A, targeting it for ubiquitination and degradation. Therefore phosphorylated CDK2-Cyclin accumulates and progression through the cell cycle is blocked. In the delayed response ATM phosphorylates the inhibitor of p53, MDM2, and p53 which is also phosphorylated by Chk2. The resulting activation and stabilization of p53 leads to an increased expression of Cdk inhibitor p21, which further helps to keep Cdk activity low and to maintain long-term cell cycle arrest.