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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.

Pubmed ID: 15916964


  • Bhoumik A
  • Takahashi S
  • Breitweiser W
  • Shiloh Y
  • Jones N
  • Ronai Z


Molecular cell

Publication Data

May 27, 2005

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 51995
  • Agency: NCI NIH HHS, Id: R01 CA099961
  • Agency: NCI NIH HHS, Id: R01 CA117927
  • Agency: NCI NIH HHS, Id: R01 CA117927-01

Mesh Terms

  • Activating Transcription Factor 2
  • Amino Acid Sequence
  • Animals
  • Antibodies, Phospho-Specific
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Checkpoint Kinase 2
  • Cyclic AMP Response Element-Binding Protein
  • DNA Damage
  • DNA Repair
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • Fibroblasts
  • Histones
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphorylation
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Radiation, Ionizing
  • Sequence Alignment
  • Serine
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Suppressor Proteins