Cited by 164DNA Repair MechanismsEffects of Radiation ExposureProtein Kinase Regulation and GTPase Signaling

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

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Adams, K E, Medhurst, A L, Dart, D A, Lakin, N D·2006·Oncogene

DOI 10.1038/sj.onc.1209426PMC PMC1852851

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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 G(1) 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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Authors: Adams, K. E., Medhurst, A. L., Dart, D. A., & Lakin, N. D.
Affiliations: University of Oxford (GB)
Corresponding author: Lakin, N D
ORCID: Dart, D A
Lakin, N D
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2006-02-13
Volume: 25
Issue: 28
Pages: 3894-3904
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1209426
PMC: PMC1852851
OpenAlex: W2008280357
Cited by: 164
References: 62
Citations by year: 2025: 5 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 11 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 10 · 2013: 10 · 2012: 9
FWCI: 8.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: Cancer Research Institute
Wellcome Trust
Cancer Research UK (A5207)
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: ATR kinase, ATM kinase, ionizing radiation, DNA damage signaling, MRN complex, MRE11, RAD50, NBS1, single-stranded DNA, nuclear foci, G1 phase, S phase, DNA double-strand breaks
MeSH terms: MRE11 Homologue Protein, Animals, Base Sequence, DNA Damage, DNA-Binding Proteins, DNA, Single-Stranded, HeLa Cells, Humans, Radiation, Ionizing, S Phase, 3T3 Cells, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, RNA, Small Interfering, DNA Repair Enzymes, Mice, Ataxia Telangiectasia Mutated Proteins

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

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