ATM acts downstream of ATR in the DNA damage response signaling of bystander cells

Susanne Burdak-Rothkamm*, Kai Rothkamm, Kevin M. Prise

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In directly irradiated cells, ATR, ATM, and DNA-dependent protein kinase (DNA-PK) deficiency resulted in reduced cell survival as predicted by the known important role of these proteins in sensing DNA damage. A decrease in clonogenic survival was also observed in ATR/ATM/DNA-PK-proficient, nonirradiated bystander cells, but this effect was completely abrogated in ATR and ATM but not DNA-PK-deficient bystander cells. ATM activation in bystander cells was found to be dependent on ATR function. Furthermore, the induction and colocalization of ATR, 53BP1, ATM-S1981P, p21, and BRCA1 foci in nontargeted cells was shown, suggesting their involvement in bystander DNA damage signaling and providing additional potential targets for its modulation. 53BP1 bystander foci were induced in an ATR-dependent manner predominantly in S-phase cells, similar to γH2AX foci induction. In conclusion, these results provide a rationale for the differential modulation of targeted and nontargeted effects of radiation.

Original languageEnglish
Pages (from-to)7059-7065
Number of pages7
JournalCancer Research
Issue number17
Publication statusPublished - 1 Sep 2008


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