The change in protein structure stimulates intermolecular autophosphorylation on Ser1981, resulting in dissociation of the dimer, and consequent Folic acid Edrophonium chloride Activation of the kinase. Full activation of ATM requires interaction with the MRN complex, which enhances the recruitment of ATM to the site of DNA damage. Proteins identified as ATM substrates regulate recruitment of DNA repair complexes, activate checkpoint responses to block cell proliferation, or induce apoptosis . Despite the well-established role of MYC in activating p53-dependent apoptosis, the exact role of MYC in regulating the DNA damage response remains poorly understood. To identify the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway in response to genotoxic stress, we have used Rat1 cells with different myc status: the parental TGR-1 cells expressing physiological levels of Myc, the myc null cells HO15.19, and the HOmyc3 cells, where expression of the murine myc has been reconstituted. We demonstrate that myc deletion impairs activation of the ATM dependent DNA damage checkpoint responses in cells exposed to ionizing radiation or the cytolethal distending toxin, including impaired phosphorylation of ATM and its downstream target H2AX, and reduced nuclear foci formation of the MRN complex. The role of MYC in the regulation of the ATM-dependent responses to genotoxin agents was further confirmed in the HCT116 cell line, where the endogenous levels of MYC were knocked down by specific siRNA. These data contribute to the understanding of the function of MYC as a regulator of the ATM-dependent checkpoint responses in response to irradiation or intoxication with CDT. Activation of checkpoint responses to genotoxic stress is one of the main barriers to prevent carcinogenesis. The fate of the cell exposed to DNA damaging agents is either cell cycle arrest, eventually followed by senescence, or apoptosis. Physiological levels of Myc trigger apoptosis in TGR-1 cells exposed to DNA damaging agents via activation of the proapoptotic proteins Bax and PKC.