Ionizing radiation activates the ATM kinase throughout the cell cycle

The ATM protein kinase is a critical intermediate in a number of cellular r esponses to ionizing irradiation (IR) and possibly other stresses. ATM dysf unction results in abnormal checkpoint responses in multiple phases of the cell cycle, including ct, S and G2, Though downstream targets of the ATM ki nase are still being elucidated. it has been demonstrated that ATM acts ups tream of p53 in a signal transduction pathway initiated by IR and can phosp horylate p53 at serine 15. The cell cycle stage-specificity of ATM activati on and p53Ser15 phosphorylation was investigated in normal lymphoblastoid c ell line (GM536). Ionizing radiation was found to enhance the kinase activi ty of ATM in all phases of the cell cycle. This enhanced activity was appar ent immediately after treatment of cells with IR, but was not accompanied b y a change in the abundance of the ATM protein. Since IR activates the ATM kinase in all phases of the cell cycle, DNA replication-dependent strand br eaks are not required for this activation. Further, since p53 protein is no t directly required for IR-induced S and GZ-phase checkpoints, the ATM kina se likely has different functional targets in different phases of the cell cycle. These observations indicate that the ATM kinase is necessary primari ly for the immediate response to DNA damage incurred in all phases of the c ell cycle.