ATM-dependent phosphorylation of ATF2 is required for the DNA damage response

Anindita Bhoumik, Shoichi Takahashi, Wolfgang Breitweiser, Yosef Shiloh, Nic Jones, Ze'ev Ronai

Research output: Contribution to journalArticlepeer-review

Abstract

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 ATF2490/8 reveal dose- and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with γ-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.

Original languageEnglish
Pages (from-to)577-587
Number of pages11
JournalMolecular Cell
Volume18
Issue number5
DOIs
StatePublished - 27 May 2005

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