ATM-Dependent Phosphorylation of ATF2 Is Required for the DNA Damage Response
Copyright policy )ATM-Dependent Phosphorylation of ATF2 Is Required for the DNA Damage Response
Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR). Phosphoantibodies to ATF2(490/8) reveal dose- and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with gamma-H2AX and MRN components into IR-induced foci (IRIF). Inhibition of ATF2 expression decreased recruitment of Mre11 to IRIF, abrogated S phase checkpoint, reduced activation of ATM, Chk1, and Chk2, and impaired radioresistance. ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity.
- Tel Aviv University Israel
- Sanford Burnham Prebys Medical Discovery Institute United States
- Cancer Research UK Manchester Institute United Kingdom
MRE11 Homologue Protein, Activating Transcription Factor 2, DNA Repair, Molecular Sequence Data, Cell Cycle Proteins, Cell Biology, Ataxia Telangiectasia Mutated Proteins, Fibroblasts, Cell Line, DNA-Binding Proteins, Histones, Checkpoint Kinase 2, Mice, DNA Repair Enzymes, Checkpoint Kinase 1, Animals, Humans, Amino Acid Sequence, Cyclic AMP Response Element-Binding Protein, Molecular Biology, Antibodies, Phospho-Specific, DNA Damage
MRE11 Homologue Protein, Activating Transcription Factor 2, DNA Repair, Molecular Sequence Data, Cell Cycle Proteins, Cell Biology, Ataxia Telangiectasia Mutated Proteins, Fibroblasts, Cell Line, DNA-Binding Proteins, Histones, Checkpoint Kinase 2, Mice, DNA Repair Enzymes, Checkpoint Kinase 1, Animals, Humans, Amino Acid Sequence, Cyclic AMP Response Element-Binding Protein, Molecular Biology, Antibodies, Phospho-Specific, DNA Damage
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