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Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex

Oncogene volume 25, pages 3894–3904 (2006)Cite this article

Abstract

ATM and ATR are two related kinases essential for signalling DNA damage. Although ATM is thought to be the principle kinase responsible for signalling ionising radiation (IR)-induced DNA damage, ATR also contributes to signalling this form of genotoxic stress. However, the molecular basis of differential ATM and ATR activation in response to IR remains unclear. Here, we report that ATR is recruited to sites of IR-induced DNA damage significantly later than activation of ATM. We show that ATR is recruited to IR-induced nuclear foci in G1 and S phase of the cell cycle, supporting a role for ATR in detecting DNA damage outside of S phase. In addition, we report that recruitment of ATR to sites of IR-induced DNA damage is concomitant with appearance of large tracts of single-stranded DNA (ssDNA) and that this event is dependent on ATM and components of the Mre11/Rad50/Nbs1 (MRN) protein complex.

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Acknowledgements

We thank GC Smith (KuDOS Pharmaceuticals Ltd, Cambridge, UK) for providing KU55933 and SP Jackson (Wellcome Trust and Cancer Research UK Gurdon Institute, Cambridge, UK) for communicating unpublished data. We are grateful to P Nghiem and L Cox for reagents in addition to members of the Lakin laboratory for comments during the preparation of this manuscript. This work was supported by Cancer Research UK and the Medical Research Council. While this manuscript was under review, reports by Garcia-Muse and Boulton, in addition to Jazayeri et al., illustrated that Mre11 is required for ATR-mediated signaling in response to IR. Furthermore, Jazayeri et al. reported that this event is also dependent on ATM.

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  1. Department of Biochemistry, University of Oxford, Oxford, UK

    K E Adams, A L Medhurst, D A Dart & N D Lakin

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  1. K E Adams
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Correspondence to N D Lakin.

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Adams, K., Medhurst, A., Dart, D. et al. Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex. Oncogene 25, 3894–3904 (2006). https://doi.org/10.1038/sj.onc.1209426

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