The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
ATR‐dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling
Open accessAbstract
The phosphatidyl inositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) regulate parallel damage response signalling pathways. ATM is reported to be activated by DNA double-strand breaks (DSBs), whereas ATR is recruited to single-stranded regions of DNA. Although the two pathways were considered to function independently, recent studies have demonstrated that ATM functions upstream of ATR following exposure to ionising radiation (IR) in S/G2. Here, we show that ATM phosphorylation at Ser1981, a characterised autophosphorylation site, is ATR-dependent and ATM-independent following replication fork stalling or UV treatment. In contrast to IR-induced ATM-S1981 phosphorylation, UV-induced ATM-S1981 phosphorylation does not require the Nbs1 C-terminus or Mre11. ATR-dependent phosphorylation of ATM activates ATM phosphorylation of Chk2, which has an overlapping function with Chk1 in regulating G2/M checkpoint arrest. Our findings provide insight into the interplay between the PIKK damage response pathways.
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“In contrast to the IR situation, UV-induced ATM phosphorylation at Serine 1981 does not require the MRN complex, which is a requirement for ATM activation by DSBs.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [144]
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“ATR-dependent ATM activation promotes Chk2 phosphorylation downstream of the checkpoint signaling [144].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [144]
In the citing paper
“ATM auto-phosphorylation at Ser1981 is ATR-dependent and ATM-independent in response to stalled DNA replication forks or UV-induced DNA damage [144].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [144]
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Citations
Cites
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Zou, L., & Elledge, S. J. (2003) · Science · doi:10.1126/science.1083430 · Cited by 2,693
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00610-2 · Cited by 2,098
Genomic Instability in Mice Lacking Histone H2AX
Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., et al. (2002) · Science · doi:10.1126/science.1069398 · Cited by 1,385
Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase
Matsuoka, S. (1998) · Science · doi:10.1126/science.282.5395.1893 · Cited by 1,322
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
Falck, J., Coates, J., & Jackson, S. P. (2005) · Nature · doi:10.1038/nature03442 · Cited by 1,304
Hickson, I., Zhao, Y., Richardson, C. J., Green, S. J., Martin, N. M. B., Orr, A. I., Reaper, P. M., Jackson, S. P., Curtin, N. J., & Smith, G. C. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2727 · Cited by 1,220
Requirement of the MRN complex for ATM activation by DNA damage
Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., & Shiloh, Y. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg541 · Cited by 1,075
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G. C. M., Lukas, J., & Jackson, S. P. (2006) · Nature Cell Biology · doi:10.1038/ncb1337 · Cited by 1,064
Cited by
Sorted by citations
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response
Blackford, A. N., & Jackson, S. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.015 · Cited by 2,050
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798
The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649
Bonner, W. M., Redon, C. E., Dickey, J. S., Nakamura, A. J., Sedelnikova, O. A., Solier, S., & Pommier, Y. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2523 · Cited by 1,623
γH2AX: a sensitive molecular marker of DNA damage and repair
Mah, L.-J., El-Osta, A., & Karagiannis, T. C. (2010) · Leukemia · doi:10.1038/leu.2010.6 · Cited by 1,557
Metadata
- Authors
- Stiff, T., Walker, S. A., Cerosaletti, K., Goodarzi, A. A., Petermann, E., Concannon, P., O'Driscoll, M., & Jeggo, P. A.
- Affiliations
- University of Sussex (GB)
- Benaroya Research Institute (US)
- Corresponding author
- Jeggo, Penny A
- Venue
- The EMBO Journal
- Published
- 2006-11-23
- Volume
- 25
- Issue
- 24
- Pages
- 5775-5782
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1698893
- OpenAlex
- W2018458310
- Cited by
- 360
- References
- 31
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 12 · 2020: 11 · 2019: 18 · 2018: 11 · 2017: 17 · 2016: 14 · 2015: 20 · 2014: 20 · 2013: 29 · 2012: 27
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Funders
- National Cancer Institute (CA 57569, R01CA057569)
- 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
- ATM, ATR, ATM phosphorylation, replication fork stalling, UV-induced DNA damage, Chk2 phosphorylation, NBS1, MRE11, DNA double-strand breaks, single-stranded DNA
- MeSH terms
- Checkpoint Kinase 1, Animals, DNA Replication, DNA-Binding Proteins, Enzyme Activation, Fibroblasts, Histones, Humans, Hydroxyurea, Mitosis, Models, Biological, Nuclear Proteins, Phosphoproteins, Phosphorylation, Phosphoserine, Protein Kinases, Ultraviolet Rays, G2 Phase, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Cell Cycle Proteins, Tumor Suppressor Proteins, Mice, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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