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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Toxicol Appl Pharmacol. 2022 May 2;446:116042. doi: 10.1016/j.taap.2022.116042

Figure 1.

Figure 1.

ATM activation by DNA double-strand breaks. Following DNA double strand breaks (DSBs) induced either by endogenous or exogenous agents, the MRN (MRE11-RAD50-NBN) complex is recruited to DSBs. In the absence of DNA damage, protein phosphatase A (PP2A) binds to ATM and prevents in activation. As a result, ATM is present as an inactive dimer. In the event of DSBs, ATM is recruited by the MRN to sites of DNA damage and undergoes rapid autophosphorylation of serine 1981 which dissociates ATM dimers and initiates ATM kinase activity. Downstream substrates of ATM include CHEK2 and P53, which induces expression of CDKN1A. ATM can also phosphorylate histone H2AX, which in turn can recruit more DNA repair factors to sites of DNA damage. The MRN complex promotes high fidelity DNA repair by homologous recombination (HR Repair).