S1219 residue of 53BP1 is phosphorylated by ATM kinase upon DNA damage and required for proper execution of DNA damage response

Haemi Lee, Hee Jin Kwak, Il taeg Cho, Seok Hee Park, Chang Hun Lee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

53BP1 is phosphorylated by the protein kinase ATM upon DNA damage. Even though several ATM phosphorylation sites in 53BP1 have been reported, those sites have little functional implications in the DNA damage response. Here, we show that ATM phosphorylates the S1219 residue of 53BP1 in vitro and that the residue is phosphorylated in cells exposed to ionizing radiation (IR). Transfection with siRNA targeting ATM abolished IR-induced phosphorylation at this residue, supporting the theory that this process is mediated by the kinase. To determine the functional relevance of this phosphorylation event, a U2OS cell line expressing S1219A mutant 53BP1 was established. IR-induced foci formation of MDC1 and γH2AX, DNA damage signaling molecules, was reduced in this cell line, implying that S1219 phosphorylation is required for recruitment of these molecules to DNA damage sites. Furthermore, overexpression of the mutant protein impeded IR-induced G2 arrest. In conclusion, we have shown that S1219 phosphorylation by ATM is required for proper execution of DNA damage response.

Original languageEnglish
Pages (from-to)32-36
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume378
Issue number1
DOIs
StatePublished - 2 Jan 2009

Keywords

  • 53BP1
  • ATM
  • DNA damage response
  • Phosphorylation

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