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

The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.

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

Open access

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

DOI 10.1038/sj.onc.1209426PMC PMC1852851

Open this paper in CoChat — free account

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/sj.onc.1209426

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., & Siliciano, J. D. (1998) · Science · doi:10.1126/science.281.5383.1677 · Cited by 2,042
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Enhanced Phosphorylation of p53 by ATM in Response to DNA Damage
Banin, S., Moyal, L., Shieh, S.-Y., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y., et al. (1998) · Science · doi:10.1126/science.281.5383.1674 · Cited by 1,797
Chk1 and Chk2 kinases in checkpoint control and cancer
Bartek, J., & Lukas, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00110-7 · Cited by 1,513
ATM Activation by DNA Double-Strand Breaks Through the Mre11-Rad50-Nbs1 Complex
Lee, J.-H., & Paull, T. T. (2005) · Science · doi:10.1126/science.1108297 · Cited by 1,424
The hMre11/hRad50 Protein Complex and Nijmegen Breakage Syndrome: Linkage of Double-Strand Break Repair to the Cellular DNA Damage Response
Carney, J. P., Maser, R. S., Olivares, H., Davis, E. M., Le Beau, M., Yates, J. R., Hays, L., Morgan, W. F., & Petrini, J. H. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81175-7 · Cited by 1,226
Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM
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
The DNA Double-Strand Break Repair Gene hMRE11 Is Mutated in Individuals with an Ataxia-Telangiectasia-like Disorder
Stewart, G. S., Maser, R. S., Stankovic, T., Bressan, D. A., Kaplan, M. I., Jaspers, N. G. J., Raams, A., Byrd, P. J., Petrini, J. H. J., & Taylor, A. M. R. (1999) · Cell · doi:10.1016/s0092-8674(00)81547-0 · Cited by 1,060
ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation
Stiff, T., O’Driscoll, M., Rief, N., Iwabuchi, K., Löbrich, M., & Jeggo, P. A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3207 · Cited by 1,050
A role for ATR in the DNA damage-induced phosphorylation of p53
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S.-Y., Taya, Y., Prives, C., & Abraham, R. T. (1999) · Genes & Development · doi:10.1101/gad.13.2.152 · Cited by 1,046
ATR disruption leads to chromosomal fragmentation and early embryonic lethality
Brown, E. J., & Baltimore, D. (2000) · Genes & Development · doi:10.1101/gad.14.4.397 · Cited by 951
Choreography of the DNA Damage Response
Lisby, M., Barlow, J. H., Burgess, R. C., & Rothstein, R. (2004) · Cell · doi:10.1016/j.cell.2004.08.015 · Cited by 891
The MRE11 complex: at the crossroads of DNA repair and checkpoint signalling
D'Amours, D., & Jackson, S. P. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm805 · Cited by 874
A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome
O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., & Goodship, J. A. (2003) · Nature Genetics · doi:10.1038/ng1129 · Cited by 794
ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway
Lim, D.-S., Kim, S.-T., Xu, B., Maser, R. S., Lin, J., Petrini, J. H. J., & Kastan, M. B. (2000) · Nature · doi:10.1038/35007091 · Cited by 786
Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint
Tercero, J. A., & Diffley, J. F. X. (2001) · Nature · doi:10.1038/35087607 · Cited by 667
MCM Proteins in DNA Replication
Tye, B. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.649 · Cited by 666
A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication
Santocanale, C., & Diffley, J. F. X. (1998) · Nature · doi:10.1038/27001 · Cited by 663
Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase.
Celis, J. E., & Celis, A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.10.3262 · Cited by 636
Overexpression of a kinase‐inactive ATR protein causes sensitivity to DNA‐damaging agents and defects in cell cycle checkpoints
Cliby, W. A., Roberts, C. J., Cimprich, K. A., Stringer, C. M., Lamb, J. R., Schreiber, S. L., & Friend, S. H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.1.159 · Cited by 542
Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress
Tibbetts, R. S., Cortez, D., Brumbaugh, K. M., Scully, R., Livingston, D., Elledge, S. J., & Abraham, R. T. (2000) · Genes & Development · doi:10.1101/gad.851000 · Cited by 512
Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance
Brown, E. J., & Baltimore, D. (2003) · Genes & Development · doi:10.1101/gad.1067403 · Cited by 511
The Mre11 complex is required for ATM activation and the G2/M checkpoint
Carson, C. T., Schwartz, R. A., Stracker, T. H., Lilley, C. E., Lee, D. V., & Weitzman, M. D. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg630 · Cited by 502
ATM-dependent phosphorylation of nibrin in response to radiation exposure
Gatei, M., Young, D., Cerosaletti, K. M., Desai-Mehta, A., Spring, K., Kozlov, S., Lavin, M. F., Gatti, R. A., Concannon, P., & Khanna, K. (2000) · Nature Genetics · doi:10.1038/75508 · Cited by 468
A unified view of the DNA-damage checkpoint
Melo, J. A., & Toczyski, D. P. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00312-5 · Cited by 457
The Nuclease Activity of Mre11 Is Required for Meiosis but Not for Mating Type Switching, End Joining, or Telomere Maintenance
Moreau, S., Ferguson, J. R., & Symington, L. S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.556 · Cited by 447
Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice
de Klein, A., Muijtjens, M., van Os, R. P., Verhoeven, Y., Smit, B., Carr, A. M., Lehmann, A. R., & Hoeijmakers, J. H. J. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00447-4 · Cited by 443
DNA Damage-Dependent Nuclear Dynamics of the Mre11 Complex
Mirzoeva, O. K., & Petrini, J. H. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.1.281-288.2001 · Cited by 387
An ATR- and Cdc7-Dependent DNA Damage Checkpoint that Inhibits Initiation of DNA Replication
Costanzo, V., Shechter, D., Lupardus, P. J., Cimprich, K. A., Gottesman, M. E., & Gautier, J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(02)00799-2 · Cited by 355
Nuclear foci of mammalian recombination proteins are located at single-stranded DNA regions formed after DNA damage
Raderschall, E., Golub, E. I., & Haaf, T. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.1921 · Cited by 350
ATM: from gene to function
Rotman, G. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.10.1555 · Cited by 322
ATR inhibition selectively sensitizes G 1 checkpoint-deficient cells to lethal premature chromatin condensation
Nghiem, P., Park, P. K., Kim, Y.-S., Vaziri, C., & Schreiber, S. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161281798 · Cited by 290
Mutations in XRS2 and RAD50 Delay but Do Not Prevent Mating-Type Switching in Saccharomyces cerevisiae
Ivanov, E. L., Sugawara, N., White, C. I., Fabre, F., & Haber, J. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3414-3425.1994 · Cited by 243
Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models
Difilippantonio, S., Celeste, A., Fernandez-Capetillo, O., Chen, H.-T., Martin, B. R. S., Laethem, F. V., Yang, Y.-P., Petukhova, G. V., Eckhaus, M., Feigenbaum, L., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1270 · Cited by 227
Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control
Wright, J. A., Keegan, K. S., Herendeen, D. R., Bentley, N. J., Carr, A. M., Hoekstra, M. F., & Concannon, P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7445 · Cited by 226
The mRNA Surveillance Protein hSMG-1 Functions in Genotoxic Stress Response Pathways in Mammalian Cells
Brumbaugh, K. M., Otterness, D. M., Geisen, C., Oliveira, V. A., Brognard, J., Li, X., Lejeune, F., Tibbetts, R. S., Maquat, L. E., & Abraham, R. T. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.05.005 · Cited by 226
A Novel mre11 Mutation Impairs Processing of Double-Strand Breaks of DNA during Both Mitosis and Meiosis
Tsubouchi, H., & Ogawa, H. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.1.260 · Cited by 223
Phosphorylation of the Bloom's Syndrome Helicase and Its Role in Recovery from S-Phase Arrest
Davies, S. L., North, P. S., Dart, D. A., Lakin, N. D., & Hickson, I. D. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.3.1279-1291.2004 · Cited by 219
Self-citation
Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage
Helt, C. E., Cliby, W. A., Keng, P. C., Bambara, R. A., & O'Reilly, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410873200 · Cited by 216
UV-induced Ataxia-telangiectasia-mutated and Rad3-related (ATR) Activation Requires Replication Stress
Ward, I. M., Minn, K. T., & Chen, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300554200 · Cited by 212
Claspin, a Chk1-Regulatory Protein, Monitors DNA Replication on Chromatin Independently of RPA, ATR, and Rad17
Lee, J., Kumagai, A., & Dunphy, W. G. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00045-5 · Cited by 199
Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint
Hekmat-Nejad, M., You, Z., Yee, M., Newport, J. W., & Cimprich, K. A. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00855-1 · Cited by 193
Nbs1 is required for ATR‐dependent phosphorylation events
Stiff, T., Reis, C., Alderton, G. K., Woodbine, L. J., O’Driscoll, M., & Jeggo, P. A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600504 · Cited by 173
The Mre11 Nuclease Is Not Required for 5′ to 3′ Resection at Multiple HO-Induced Double-Strand Breaks
Llorente, B., & Symington, L. S. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9682-9694.2004 · Cited by 170
A requirement for replication in activation of the ATR-dependent DNA damage checkpointPreprint
Lupardus, P. J., Byun, T. S., Yee, M., Hekmat-Nejad, M., & Cimprich, K. A. (2002) · Genes & Development · doi:10.1101/gad.1013502 · Cited by 163
Distinct modes of ATR activation after replication stress and DNA double‐strand breaks in Caenorhabditis elegans
García‐Muse, T., & Boulton, S. J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600896 · Cited by 163
Recruitment of the Cell Cycle Checkpoint Kinase ATR to Chromatin during S-phase
Dart, D. A., Adams, K. E., Akerman, I., & Lakin, N. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314212200 · Cited by 124
Self-citation
The Nijmegen Breakage Syndrome Protein Is Essential for Mre11 Phosphorylation upon DNA Damage
Dong, Z., Zhong, Q., & Chen, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.28.19513 · Cited by 123
The Role of Single-stranded DNA and Polymerase α in Establishing the ATR, Hus1 DNA Replication Checkpoint
You, Z., Kong, L., & Newport, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204120200 · Cited by 114
Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway
Nakada, D., Hirano, Y., & Sugimoto, K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.10016-10025.2004 · Cited by 113
ATR Is Not Required for p53 Activation but Synergizes with p53 in the Replication Checkpoint
Nghiem, P., Park, P. K., Kim, Y.-S., Desai, B. N., & Schreiber, S. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m106113200 · Cited by 99
DNA Replication Defects, Spontaneous DNA Damage, and ATM-dependent Checkpoint Activation in Replication Protein A-deficient Cells
Dodson, G. E., Shi, Y., & Tibbetts, R. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400242200 · Cited by 96
The Mre11 complex and ATM: a two-way functional interaction in recognising and signaling DNA double strand breaks
Lavin, M. F. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.07.001 · Cited by 82
Rad50 depletion impacts upon ATR-dependent DNA damage responses
Zhong, H., Bryson, A., Eckersdorff, M., & Ferguson, D. O. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi302 · Cited by 61
Neocarzinostatin induces Mre11 phosphorylation and focus formation through an ATM- and NBS1-dependent mechanism
Yuan, S. F., Chang, H.-L., Hou, M., Chan, T., Kao, Y. H., Wu, Y., & Su, J. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00220-2 · Cited by 29
Protective packaging for DNA
Downs, J. A., & Jackson, S. P. (2003) · Nature · doi:10.1038/424732a · Cited by 20

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
DNA Damage Sensing by the ATM and ATR Kinases
Marechal, A., & Zou, L. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012716 · Cited by 1,514
Human CtIP promotes DNA end resection
Sartori, A. A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., & Jackson, S. P. (2007) · Nature · doi:10.1038/nature06337 · Cited by 1,362
The ATM–Chk2 and ATR–Chk1 Pathways in DNA Damage Signaling and Cancer
Smith, J., Tho, L. M., Xu, N., & Gillespie, D. A. (2010) · Advances in cancer research · doi:10.1016/b978-0-12-380888-2.00003-0 · Cited by 1,331

See all 164

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks