Quantitative proteomics reveal ATM kinase-dependent exchange in DNA damage response complexes

Serah Choi, Rohith Srivas, Katherine Y. Fu, Brian L. Hood, Banu Dost, Gregory A. Gibson, Simon C. Watkins, Bennett Van Houten, Nuno Bandeira, Thomas P. Conrads, Trey Ideker, Christopher J. Bakkenist*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


ATM is a protein kinase that initiates a well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However, the role for ATM in coordinating critical protein interactions and subsequent exchanges within DNA damage response (DDR) complexes is unknown. We combined SILAC-based tandem mass spectrometry and a subcellular fractionation protocol to interrogate the proteome of irradiated cells treated with or without the ATM kinase inhibitor KU55933. We developed an integrative network analysis to identify and prioritize proteins that were responsive to KU55933, specifically in chromatin, and that were also enriched for physical interactions with known DNA repair proteins. This analysis identified 53BP1 and annexin A1 (ANXA1) as strong candidates. Using fluorescence recovery after photobleaching, we found that the exchange of GFP-53BP1 in DDR complexes decreased with KU55933. Further, we found that ANXA1 knockdown sensitized cells to IR via a mechanism that was not potentiated by KU55933. Our study reveals a role for ATM kinase activity in the dynamic exchange of proteins in DDR complexes and identifies a role for ANXA1 in cellular radioprotection.

Original languageEnglish
Pages (from-to)4983-4991
Number of pages9
JournalJournal of Proteome Research
Issue number10
StatePublished - 5 Oct 2012
Externally publishedYes


  • 53BP1
  • ATM
  • DNA damage response


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