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

Adams, K. E., Medhurst, A. L., Dart, Dafydd Alwyn and Lakin, N. D. 2006. Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex. Oncogene 25 (28) , pp. 3894-3904. 10.1038/sj.onc.1209426

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Nature Publishing Group
ISSN:	0950-9232
Last Modified:	08 Jan 2020 03:29
URI:	https://orca.cardiff.ac.uk/id/eprint/50284

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