Ionizing radiation activates the ATM kinase throughout the cell cycle.
The ATM protein kinase is a critical intermediate in a number of cellular responses to ionizing irradiation (IR) and possibly other stresses. ATM dysfunction results in abnormal checkpoint responses in multiple phases of the cell cycle, including G1, S and G2. Though downstream targets of the ATM kinase are still being elucidated, it has been demonstrated that ATM acts upstream of p53 in a signal transduction pathway initiated by IR and can phosphorylate p53 at serine 15. The cell cycle stage-specificity of ATM activation and p53Ser15 phosphorylation was investigated in normal lymphoblastoid cell line (GM536). Ionizing radiation was found to enhance the kinase activity of ATM in all phases of the cell cycle. This enhanced activity was apparent immediately after treatment of cells with IR, but was not accompanied by 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 breaks are not required for this activation. Further, since p53 protein is not directly required for IR-induced S and G2-phase checkpoints, the ATM kinase likely has different functional targets in different phases of the cell cycle. These observations indicate that the ATM kinase is necessary primarily for the immediate response to DNA damage incurred in all phases of the cell cycle.
Pandita
T K
TK
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Lieberman
H B
HB
Lim
D S
DS
Dhar
S
S
Zheng
W
W
Taya
Y
Y
Kastan
M B
MB
D001260:Ataxia Telangiectasia / Q000201:enzymology* / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000528:radiation effects*; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002469:Cell Separation; D002470:Cell Survival / Q000528:radiation effects; D002498:Centrifugation; D004249:DNA Damage / Q000528:radiation effects; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000528:radiation effects; D016193:G1 Phase / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000528:radiation effects*; D011836:Radiation Tolerance; D012694:Serine / Q000378:metabolism / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D012694:Serine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases