Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM

Hickson, Ian; Zhao, Yan; Richardson, Caroline J.; Green, Sharon J.; Martin, Niall M. B.; Orr, Alisdair I.; Reaper, Philip M.; Jackson, Stephen P.; Curtin, Nicola J.; Smith, Graeme C. M.

doi:10.1158/0008-5472.can-04-2727

Cited by 1,220DNA Repair MechanismsEffects of Radiation ExposureProtein Kinase Regulation and GTPase Signaling

Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM

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Hickson, Ian, Zhao, Yan, Richardson, Caroline J., Green, Sharon J., Martin, Niall M. B., Orr, Alisdair I., Reaper, Philip M., Jackson, Stephen P. +2 more·2004·Cancer Research

DOI 10.1158/0008-5472.can-04-2727

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Abstract

The serine/threonine protein kinase ATM signals to cell cycle and DNA repair components by phosphorylating downstream targets such as p53, CHK2, NBS1, and BRCA1. Mutation of ATM occurs in the human autosomal recessive disorder ataxia-telangiectasia, which is characterized by hypersensitivity to ionizing radiation and a failure of cells to arrest the cell cycle after the induction of DNA double-strand breaks. It has thus been proposed that ATM inhibition would cause cellular radio- and chemosensitization. Through screening a small molecule compound library developed for the phosphatidylinositol 3'-kinase-like kinase family, we identified an ATP-competitive inhibitor, 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (KU-55933), that inhibits ATM with an IC(50) of 13 nmol/L and a Ki of 2.2 nmol/L. KU-55933 shows specificity with respect to inhibition of other phosphatidylinositol 3'-kinase-like kinases. Cellular inhibition of ATM by KU-55933 was demonstrated by the ablation of ionizing radiation-dependent phosphorylation of a range of ATM targets, including p53, gammaH2AX, NBS1, and SMC1. KU-55933 did not show inhibition of UV light DNA damage induced cellular phosphorylation events. Exposure of cells to KU-55933 resulted in a significant sensitization to the cytotoxic effects of ionizing radiation and to the DNA double-strand break-inducing chemotherapeutic agents, etoposide, doxorubicin, and camptothecin. Inhibition of ATM by KU-55933 also caused a loss of ionizing radiation-induced cell cycle arrest. By contrast, KU-55933 did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage. We conclude that KU-55933 is a novel, specific, and potent inhibitor of the ATM kinase.

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From USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 (2010) · cites this paper as Hickson et al., 2004

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 · see citing works
A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
Vlahos, C. J., Matter, W. F., Hui, K. Y., & Brown, R. F. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37680-9 · Cited by 3,248 · see citing works
ATM and related protein kinases: safeguarding genome integrity
Shiloh, Y. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1011 · Cited by 2,577 · see citing works
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 · see citing works
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 · see citing works
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., & Chen, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100466200 · Cited by 1,954 · see citing works
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 · see citing works
Chk1 is an essential kinase that is regulated by Atr and required for the G <sub>2</sub> /M DNA damage checkpoint
Liu, Q., Guntuku, S., Cui, X.-S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., et al. (2000) · Genes & Development · doi:10.1101/gad.14.12.1448 · Cited by 1,625 · see citing works
Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and Staurosporine
Walker, E. H., Pacold, M. E., Perišić, O., Stephens, L., Hawkins, P. T., Wymann, M. P., & Williams, R. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00089-4 · Cited by 1,211 · see citing works
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 · see citing works
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 1,010 · see citing works
Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation
Blunt, T., Finnie, N., Taccioli, G. E., Smith, G. C. M., Demengeot, J., Gottlieb, T. M., Mizuta, R., Varghese, A. J., Alt, F. W., Jeggo, P. A., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90360-7 · Cited by 865 · see citing works
Self-citation
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., & Elledge, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190030497 · Cited by 830 · see citing works
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 · see citing works
The many substrates and functions of ATM.
Kastan, M. B., & Lim, D.-S. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043058 · Cited by 779 · see citing works
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
Maya, R., Balass, M., Kim, S.-T., Shkedy, D., Leal, J.-F. M., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., et al. (2001) · Genes & Development · doi:10.1101/gad.886901 · Cited by 716 · cited 1× · see citing works
“The role of the ATM protein in the stabilization of p53 in response to DNA double-strand break-inducing agents is very well established (4, 10, 11, 13, 44).”
Background
Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3‐kinase inhibitors, wortmannin and LY294002.
Brunn, G. J., Williams, J. M., Sabers, C. J., Wiederrecht, G., Lawrence, J. C., & Abraham, R. T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00911.x · Cited by 715 · see citing works
Interfaces Between the Detection, Signaling, and Repair of DNA Damage
Rouse, J. W., & Jackson, S. P. (2002) · Science · doi:10.1126/science.1074740 · Cited by 688 · see citing works
Self-citation
THE GENETIC DEFECT IN ATAXIA-TELANGIECTASIA
Lavin, M. F., & Shiloh, Y. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.177 · Cited by 642 · see citing works
ATM and ATR: networking cellular responses to DNA damage
Shiloh, Y. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00159-3 · Cited by 601 · see citing works
Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage.
Chehab, N. H., Malikzay, A., Stavridi, E. S., & Halazonetis, T. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13777 · Cited by 583 · see citing works
Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damagePreprint
Kim, S., Xu, B., & Kastan, M. B. (2002) · Genes & Development · doi:10.1101/gad.970602 · Cited by 581 · see citing works
Involvement of Brca1 in S-Phase and G 2 -Phase Checkpoints after Ionizing Irradiation
Xu, B., Kim, S., & Kastan, M. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3445-3450.2001 · Cited by 540 · see citing works
Untitled work
(1998) · PubMed · Cited by 525 · see citing works
Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase
Ui, M., Okada, T., Hazeki, K., & Hazeki, O. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89056-8 · Cited by 519 · see citing works
Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products
Zhao, S., Weng, Y., Yuan, S. F., Lin, Y.-T., Hsu, H.-C., Lin, S. J., Gerbino, E., Song, M., Zdzienicka, M. Z., Gatti, R. A., et al. (2000) · Nature · doi:10.1038/35013083 · Cited by 483 · see citing works
Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation
Xu, B., Kim, S., Lim, D., & Kastan, M. B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1049-1059.2002 · Cited by 470 · see citing works
Cancer Chemotherapy and Biotherapy: Principles and Practice
Chabner, B. A., & Longo, D. L. (1996) · Cited by 409 · see citing works
Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1
Veuger, S. J., Curtin, N. J., Richardson, C. J., Smith, G. C. M., & Durkacz, B. W. (2003) · PubMed · doi:10.25405/ncl.34607331 · Cited by 332 · see citing works
Self-citation
ATM: from gene to function
Rotman, G. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.10.1555 · Cited by 322 · see citing works
On the Nature of a Defect in Cells from Individuals with Ataxia-Telangiectasia
Cornforth, M. N., & Bedford, J. S. (1985) · Science · doi:10.1126/science.3975628 · Cited by 296 · see citing works
ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses
Bao, S., Tibbetts, R. S., Brumbaugh, K. M., Fang, Y., Richardson, D. A., Ali, A., Chen, S. M., Abraham, R. T., & Wang, X.-F. (2001) · Nature · doi:10.1038/35082110 · Cited by 279 · see citing works
Caffeine Abolishes the Mammalian G2/M DNA Damage Checkpoint by Inhibiting Ataxia-Telangiectasia-mutated Kinase Activity
Zhou, B. S., Chaturvedi, P., Spring, K. J., Scott, S. P., Johanson, R. A., Mishra, R., Mattern, M. R., Winkler, J. D., & Khanna, K. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10342 · Cited by 278 · see citing works
ATM-related genes: What do they tell us about functions of the human gene?
Zakian, V. A. (1995) · Cell · doi:10.1016/0092-8674(95)90463-8 · Cited by 271 · see citing works
The p53-dependent G1 cell cycle checkpoint pathway and ataxia-telangiectasia.
Canman, C. E., Wolff, A. C., Chen, C.-Y., Fornace, A. J., & Kastan, M. B. (1994) · PubMed · Cited by 246 · see citing works
Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks
Foray, N. (1997) · International Journal of Radiation Biology · doi:10.1080/095530097143266 · Cited by 205 · see citing works
Cancer Chemotherapy and Biotherapy : Principles and Practice
Burney, I. A. (2011) · Sultan Qaboos University medical journal · doi:10.18295/2075-0528.1308 · Cited by 185 · see citing works
Competitive and noncompetitive inhibition of the DNA-dependent protein kinase.
Izzard, R. A., Jackson, S. P., & Smith, G. C. M. (1999) · PubMed · Cited by 177 · see citing works
Self-citation
Enhanced radiation and chemotherapy-mediated cell killing of human cancer cells by small inhibitory RNA silencing of DNA repair factors.
Collis, S. J., Swartz, M. J., Nelson, W. G., & DeWeese, T. L. (2003) · PubMed · Cited by 157 · see citing works
Rejoining of Double Strand Breaks in Normal Human and Ataxia-telangiectasia Fibroblasts after Exposure to60Co γ-rays,241Am α-particles or Bleomycin
Coquerelle, T. M., Weibezahn, K. F., & Lücke‐Huhle, C. (1987) · International Journal of Radiation Biology and Related Studies in Physics Chemistry and Medicine · doi:10.1080/09553008714550711 · Cited by 114 · see citing works
Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine
Block, W. D. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh508 · Cited by 90 · see citing works
p53-dependent apoptosis or growth arrest induced by different forms of radiation in U2OS cells: p21WAF1/CIP1 repression in UV induced apoptosis
Allan, L. A., & Fried, M. (1999) · Oncogene · doi:10.1038/sj.onc.1202931 · Cited by 83 · see citing works
Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents.
Jaspers, N. G. J., de Wit, J., Regulski, M., & Bootsma, D. (1982) · PubMed · Cited by 78 · see citing works
ATM as a target for novel radiosensitizers
Sarkaria, J. N., & Eshleman, J. S. (2001) · Seminars in Radiation Oncology · doi:10.1053/srao.2001.26030 · Cited by 64 · see citing works
Normal repair of DNA single-strand breaks in patients with ataxia telangiectasia
Fornace, A. J., & Little, J. B. (1980) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(80)90153-7 · Cited by 62 · see citing works
Enhanced Sensitivity to Camptothecin in Ataxia-telangiectasia Cells and Its Relationship with the Expression of DNA Topoisomerase I
Smith, P. J., Makinson, T. A., & Watson, J. V. (1989) · International Journal of Radiation Biology · doi:10.1080/09553008914550271 · Cited by 59 · see citing works
Loss of atm sensitises p53-deficient cells to topoisomerase poisons and antimetabolites
Fedier, A., Schlamminger, M., Schwarz, V. A., Haller, U., Howell, S. B., & Fink, D. A. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg240 · Cited by 45 · see citing works
Kinetics of O6-methylguanine repair in human normal and ataxia telangiectasia cell lines and correlation of repair capacity with cellular sensitivity to methylating agents.
Shiloh, Y., & Becker, Y. (1981) · PubMed · Cited by 43 · see citing works
Hypersensitivity of Cultured Ataxia-Telangiectasia Cells to Etoposide 2
Henner, W. D., & Blazka, M. E. (1986) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/76.6.1007 · Cited by 38 · see citing works
Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors
Guha, C., Guha, U., Tribius, S., Alfieri, A. A., Casper, D., Chakravarty, P. K., Mellado, W., Pandita, T. K., & Vikram, B. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301174 · Cited by 35 · see citing works
Ataxia telangiectasia mutated deficiency affects astrocyte growth but not radiosensitivity.
Gosink, E. C., Chong, M. J., & McKinnon, P. J. (1999) · PubMed · Cited by 34 · see citing works
Repair of strand breaks in superhelical dna of ataxia telangiectasia lymphoblastoid cells
Lavin, M. F., & Davidson, M. M. (1981) · Journal of Cell Science · doi:10.1242/jcs.48.1.383 · Cited by 34 · see citing works
An anti-sense construct of full-length ATM cDNA imposes a radiosensitive phenotype on normal cells
Zhang, N., Chen, P., Gatei, M. H., Scott, S. P., Khanna, K. K., & Lavin, M. F. (1998) · Oncogene · doi:10.1038/sj.onc.1202007 · Cited by 33 · see citing works
Characterization of Recombinant Phosphatidylinositol 4-Kinase β Reveals Auto- and Heterophosphorylation of the Enzyme
Zhao, X., Bondeva, T., & Balla, T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14642 · Cited by 27 · see citing works
Hypersensitivity of lymphoblastoid lines derived from ataxia telangiectasia patients to the induction of chromosomal aberrations by etoposide (VP-16)
Caporossi, D., Porfirio, B., Nicoletti, B., Palitti, F., Degrassi, F., Salvia, R. D., & Tanzarella, C. (1993) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(93)90167-e · Cited by 21 · see citing works
siRNA-silencing of DNA repair factors results in enhanced radiation and chemotherapy-mediated killing of human cancer cells
Collis, S. J., Swartz, M., & DeWeese, T. L. (2003) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(03)00904-0 · Cited by 21 · see citing works
Human fibroblasts transfected with an ATM antisense vector respond abnormally to ionizing radiation.
Uhrhammer, N. A., Fritz, E., Boyden, L. M., & Meyn, M. S. (1999) · International Journal of Molecular Medicine · doi:10.3892/ijmm.4.1.43 · Cited by 11 · see citing works

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Topoisomerase I inhibitors: camptothecins and beyond
Pommier, Y. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1977 · Cited by 2,295 · see citing works
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Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986 · see citing works
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Bunting, S. F., Callén, E., Wong, N., Chen, H.-T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010) · Cell · doi:10.1016/j.cell.2010.03.012 · Cited by 1,671 · see citing works
Targeting the DNA Damage Response in Cancer
O’Connor, M. J. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.040 · Cited by 1,551 · see citing works
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Yang, L., Besschetnova, T. Y., Brooks, C. R., Shah, J. V., & Bonventre, J. V. (2010) · Nature Medicine · doi:10.1038/nm.2144 · Cited by 1,333 · see citing works
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Shrivastav, M., De Haro, L. P., & Nickoloff, J. A. (2008) · Cell Research · doi:10.1038/cr.2007.111 · Cited by 1,329 · see citing works
Deficiency in the Repair of DNA Damage by Homologous Recombination and Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition
McCabe, N., Turner, N. C., Lord, C. J., Kluzek, K., Białkowska, A., Swift, S., Giavara, S., O’Connor, M. J., Tutt, A. N. J., Zdzienicka, M. Z., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0140 · Cited by 1,311 · see citing works
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Raab, M., Gentili, M., Belly, H. D., Thiam, H. R., Vargas, P., Jiménez, A. J., Lautenschläger, F., Voituriez, R., Lennon‐Duménil, A., Manel, N., et al. (2016) · Science · doi:10.1126/science.aad7611 · Cited by 946 · see citing works
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Toledo, L. I., Altmeyer, M., Rask, M.-B., Lukas, C., Larsen, D. H., Povlsen, L. K., Bekker-Jensen, S., Mailand, N., Bartek, J., & Lukas, J. (2013) · Cell · doi:10.1016/j.cell.2013.10.043 · Cited by 911 · see citing works
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Kolas, N. K., Chapman, J. R., Nakada, S., Ylanko, J., Chahwan, R., Sweeney, F. D., Panier, S., Mendez, M., Wildenhain, J., Thomson, T. M., et al. (2007) · Science · doi:10.1126/science.1150034 · Cited by 900 · see citing works
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Self-citation
ATM-Dependent Chromatin Changes Silence Transcription In cis to DNA Double-Strand Breaks
Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., & Greenberg, R. A. (2010) · Cell · doi:10.1016/j.cell.2010.04.038 · Cited by 737 · see citing works
Non-transcriptional control of DNA replication by c-Myc
Dominguez-Sola, D., Ying, C. Y., Grandori, C., Ruggiero, L., Chen, B., Li, M., Galloway, D. A., Gu, W. J., Gautier, J., & Dalla‐Favera, R. (2007) · Nature · doi:10.1038/nature05953 · Cited by 652 · see citing works
ATM and ATR as therapeutic targets in cancer
Weber, A. M., & Ryan, A. J. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.001 · Cited by 644 · see citing works
Biological response of cancer cells to radiation treatment
Baskar, R., Dai, J., Nei, W. L., Yeo, R., & Yeoh, K. (2014) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2014.00024 · Cited by 638 · see citing works
USP10 Regulates p53 Localization and Stability by Deubiquitinating p53
Yuan, J., Luo, K., Zhang, L., Cheville, J. C., & Lou, Z. (2010) · Cell · doi:10.1016/j.cell.2009.12.032 · Cited by 637 · see citing works
“To examine whether USP10 protein becomes USP10 p53 p21 BAX b-actin IR: 0 2 4 24 0 2 4 24 (hrs) Ctrl USP10 - IR LMB IR+LMB IR+Ku55933 USP10 DAPI Merge USP10 MAX C N C N C N C N IR: - + - + HCT116 p53+/+ HCT116 p53-/-”
Influential
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors
Brown, J. S., O’Carrigan, B., Jackson, S. P., & Yap, T. A. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0860 · Cited by 623 · see citing works
Self-citation
4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1
Menear, K. A., Adcock, C., Boulter, R., Cockcroft, X. F., Copsey, L., Cranston, A. N., Dillon, K. J., Drzewiecki, J., Garman, S., Gomez, S., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8001263 · Cited by 604 · see citing works
Self-citation
The DNA Damage Response: Implications for Tumor Responses to Radiation and Chemotherapy
Goldstein, M., & Kastan, M. B. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-081313-121208 · Cited by 590 · see citing works
Chromosome Segregation Errors as a Cause of DNA Damage and Structural Chromosome Aberrations
Janssen, A., van der Burg, M. J., Szuhai, K., Kops, G. J. P. L., & Medema, R. H. (2011) · Science · doi:10.1126/science.1210214 · Cited by 582 · see citing works
Trex1 Exonuclease Degrades ssDNA to Prevent Chronic Checkpoint Activation and Autoimmune Disease
Yang, Y., Lindahl, T. L., & Barnes, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.10.017 · Cited by 574 · see citing works
Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
Patel, A. G., Sarkaria, J. N., & Kaufmann, S. H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013715108 · Cited by 543 · see citing works
Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks
Galanty, Y., Belotserkovskaya, R., Coates, J., Polo, S. E., Miller, K. M., & Jackson, S. P. (2009) · Nature · doi:10.1038/nature08657 · Cited by 520 · see citing works
Self-citation
Effects of Non-Thermal Plasma on Mammalian Cells
Kalghatgi, S. R., Kelly, C. M., Cerchar, E., Torabi, B., Alekseev, O., Fridman, A., Friedman, G., & Azizkhan‐Clifford, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016270 · Cited by 508 · see citing works
Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair
Berkovich, E., Monnat, R. J., & Kastan, M. B. (2007) · Nature Cell Biology · doi:10.1038/ncb1599 · Cited by 477 · see citing works
Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer
Juvekar, A., Burga, L. N., Hu, H., Lunsford, E. P., Ibrahim, Y. H., Balmañà, J., Rajendran, A., Papa, A., Spencer, K., Lyssiotis, C. A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0336 · Cited by 465 · see citing works
A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations
Toledo, L. I., Murga, M., Zur, R., Soria, R., Rodriguez, A., Martinez, S., Oyarzabal, J., Pastor, J., Bischoff, J. R., & Fernandez-Capetillo, O. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2076 · Cited by 465 · see citing works
Strategies for optimizing the response of cancer and normal tissues to radiation
Moding, E. J., Kastan, M. B., & Kirsch, D. G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4003 · Cited by 461 · see citing works
ATM-ATR–dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype
Soriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., Di Gialleonardo, V., Cippitelli, M., Fionda, C., Petrucci, M. T., Guarini, A., et al. (2009) · Blood · doi:10.1182/blood-2008-08-173914 · Cited by 460 · see citing works
Preclinical Evaluation of a Potent Novel DNA-Dependent Protein Kinase Inhibitor NU7441
Zhao, Y., Thomas, H. D., Batey, M. A., Cowell, I. G., Richardson, C. J., Griffin, R. J., Calvert, H., Newell, D. R., Smith, G. C. M., & Curtin, N. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4275 · Cited by 447 · see citing works
Self-citation
Analysis of protein dynamics at active, stalled, and collapsed replication forksPreprint
Sirbu, B. M., Couch, F. B., Feigerle, J. T., Bhaskara, S., Hiebert, S. W., & Cortez, D. (2011) · Genes & Development · doi:10.1101/gad.2053211 · Cited by 430 · see citing works
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group (2010) · Nature Genetics · doi:10.1038/ng.735 · Cited by 448 · see citing works
ATM stabilizes DNA double-strand-break complexes during V(D)J recombination
Bredemeyer, A. L., Sharma, G. G., Huang, C., Helmink, B. A., Walker, L. M., Khor, K. C., Nuskey, B., Sullivan, K. E., Pandita, T. K., Bassing, C. H., et al. (2006) · Nature · doi:10.1038/nature04866 · Cited by 425 · see citing works
A forward chemical genetic screen reveals an inhibitor of the Mre11–Rad50–Nbs1 complex
Dupré, A., Boyer-Châtenet, L., Sattler, R. M., Modi, A. P., Lee, J., Nicolette, M. L., Kopelovich, L., Jasin, M., Baer, R. J., Paull, T. T., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.63 · Cited by 416 · see citing works
Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization
Maier, P., Hartmann, L., Wenz, F. K., & Herskind, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17010102 · Cited by 417 · see citing works
γH2AX and MDC1: Anchoring the DNA-damage-response machinery to broken chromosomes
Stucki, M., & Jackson, S. P. (2006) · DNA Repair · doi:10.1016/j.dnarep.2006.01.012 · Cited by 412 · see citing works
Self-citation
Requirement of ATM-Dependent Monoubiquitylation of Histone H2B for Timely Repair of DNA Double-Strand Breaks
Moyal, L., Lerenthal, Y., Gana‐Weisz, M., Mass, G., So, S., Wang, S., Eppink, B., Chung, Y. M., Shalev, G., Shema, E., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.015 · Cited by 402 · see citing works
ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cellsPreprint
Yazinski, S. A., Comaills, V., Buisson, R., Genois, M., Nguyen, H. D., Ho, C. K., Kwan, T. T., Morris, R. T., Lauffer, S., Nussenzweig, A., et al. (2017) · Genes & Development · doi:10.1101/gad.290957.116 · Cited by 393 · see citing works
Human Papillomaviruses Activate the ATM DNA Damage Pathway for Viral Genome Amplification upon Differentiation
Moody, C. A., & Laimins, L. A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000605 · Cited by 382 · see citing works
Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion
Golding, S. E., Rosenberg, E., Valerie, N. C. K., Hussaini, I. M., Frigerio, M., Cockcroft, X. F., Chong, W. Y., Hummersone, M., Rigoreau, L. J. M., Menear, K. A., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0519 · Cited by 385 · see citing works
DNA repair targeted therapy: The past or future of cancer treatment?
Gavande, N. S., VanderVere-Carozza, P. S., Hinshaw, H. D., Jalal, S. I., Sears, C. R., Pawelczak, K. S., & Turchi, J. J. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.02.003 · Cited by 387 · see citing works
DNA Repair Pathways in Cancer Therapy and Resistance
Li, L.-Y., Guan, Y.-D., Chen, X.-S., Yang, J.-M., & Cheng, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.629266 · Cited by 383 · see citing works
“…been reported that human tumor cells treated with KU-55933, a specific inhibitor of the ATM kinase, could sensitize tumor cells to the cytotoxic effects of IR and DNA DSBs-inducing chemotherapeutic agents such as etoposide, doxorubicin, and camptothecin (Hickson et al., 2004; Hoey et al., 2018).”
Background
Regulation of DNA‐damage responses and cell‐cycle progression by the chromatin remodelling factor CHD4
Polo, S. E., Kaidi, A., Baskcomb, L., Galanty, Y., & Jackson, S. P. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.188 · Cited by 374 · see citing works
“Furthermore, we found that this CHD4 phosphorylation was prevented when cells were incubated with Wortmannin (Sarkaria et al, 1998) or the ATM inhibitor KU-55933 (Hickson et al, 2004), but not the DNA-PK inhibitor NU-7441 (Leahy et al, 2004) (see Figure 3B; Supplementary Figure S4B).”
BackgroundMethodInfluentialSelf-citation
Mechanisms of double-strand break repair in somatic mammalian cells
Hartlerode, A. J., & Scully, R. (2009) · Biochemical Journal · doi:10.1042/bj20090942 · Cited by 365 · see citing works
ATR‐dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling
Stiff, T., Walker, S. A., Cerosaletti, K., Goodarzi, A. A., Petermann, E., Concannon, P., O'Driscoll, M., & Jeggo, P. A. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601446 · Cited by 360 · see citing works
Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography
Thompson, L. H. (2012) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2012.06.002 · Cited by 357 · see citing works
G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer
Bucher, N., & Britten, C. D. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604208 · Cited by 348 · see citing works
RETRACTED: hnRNP K: An HDM2 Target and Transcriptional Coactivator of p53 in Response to DNA Damage
Moumen, A., Masterson, P., O'Connor, M. J., & Jackson, S. P. (2005) · Cell · doi:10.1016/j.cell.2005.09.032 · Cited by 350 · see citing works
Self-citation
Retracted
Screen for DNA‐damage‐responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells
Tjeertes, J. V., Miller, K. M., & Jackson, S. P. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.119 · Cited by 347 · see citing works
Self-citation
Replication stress induces 53BP1-containing OPT domains in G1 cells
Harrigan, J. A., Belotserkovskaya, R., Coates, J., Dimitrova, D. S., Polo, S. E., Bradshaw, C. R., Fraser, P., & Jackson, S. P. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201011083 · Cited by 336 · see citing works
Self-citation
Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition
Ferguson, L. R., Chen, H., Collins, A. R., Connell, M., Damia, G. L. M., Dasgupta, S., Malhotra, M., Meeker, A. K., Amedei, A., Amin, A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.005 · Cited by 340 · see citing works
Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response
Beli, P., Lukashchuk, N., Wagner, S., Weinert, B. T., Olsen, J. V., Baskcomb, L., Mann, M., Jackson, S. P., & Choudhary, C. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.026 · Cited by 331 · see citing works
Self-citation
Radiation-induced cell signaling: inside-out and outside-in
Valerie, K. C., Yacoub, A., Hagan, M. P., Curiel, D. T., Fisher, P. B., Grant, S., & Dent, P. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0596 · Cited by 329 · see citing works
Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1
Nakada, S., Tai, I., Panier, S., Al-Hakim, A., Iemura, S.-I., Juang, Y.-C., O’Donnell, L., Kumakubo, A., Munro, M., Sicheri, F., et al. (2010) · Nature · doi:10.1038/nature09297 · Cited by 357 · see citing works
DNA damage checkpoint kinases in cancer
Smith, H. L., Southgate, H. E. D., Tweddle, D. A., & Curtin, N. J. (2020) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2020.3 · Cited by 323 · see citing works
Self-citation
A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor
Turner, N. C., Lord, C. J., Iorns, E. J., Brough, R., Swift, S., Elliott, R. J. R., Rayter, S., Tutt, A. N. J., & Ashworth, A. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.61 · Cited by 322 · see citing works
DNA damage signaling in response to double-strand breaks during mitosis
Giunta, S., Belotserkovskaya, R., & Jackson, S. P. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200911156 · Cited by 321 · see citing works
Self-citation
H2AX: functional roles and potential applications
Dickey, J. S., Redon, C. E., Nakamura, A. J., Baird, B. J., Sedelnikova, O. A., & Bonner, W. M. (2009) · Chromosoma · doi:10.1007/s00412-009-0234-4 · Cited by 320 · see citing works
Rescue of Hippo coactivator YAP1 triggers DNA damage–induced apoptosis in hematological cancers
Cottini, F., Hideshima, T., Xu, C., Sattler, M., Dori, M., Agnelli, L., ten Hacken, E., Bertilaccio, M. T. S., Antonini, E., Neri, A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3562 · Cited by 310 · see citing works
The combined status of ATM and p53 link tumor development with therapeutic responsePreprint
Jiang, H., Reinhardt, H. C., Bártková, J., Tommiska, J., BLOMQVIST, C. P., Nevanlinna, H. A., Bártek, J., Yaffe, M. B., & Hemann, M. T. (2009) · Genes & Development · doi:10.1101/gad.1815309 · Cited by 303 · see citing works
ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks
Lavin, M. F. (2007) · Oncogene · doi:10.1038/sj.onc.1210880 · Cited by 301 · see citing works
The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo
Weston, V., Oldreive, C., Skowrońska, A., Oscier, D. G., Pratt, G., Dyer, M. J. S., Smith, G. C. M., Powell, J. E., Rudzki, Z., Kearns, P. R., et al. (2010) · Blood · doi:10.1182/blood-2010-01-265769 · Cited by 300 · see citing works
Self-citation
Activation of the Cellular DNA Damage Response in the Absence of DNA Lesions
Soutoglou, E., & Misteli, T. (2008) · Science · doi:10.1126/science.1159051 · Cited by 299 · see citing works
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN
Arnoult, N., Correia, A., Ma, J., Merlo, A., Garcia-Gomez, S., Maric, M., Tognetti, M., Benner, C. W., Boulton, S. J., Saghatelian, A., et al. (2017) · Nature · doi:10.1038/nature24023 · Cited by 299 · see citing works
Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis
Cerboni, C., Zingoni, A., Cippitelli, M., Piccoli, M., Frati, L., & Santoni, A. (2007) · Blood · doi:10.1182/blood-2006-10-052720 · Cited by 296 · see citing works
Chk1 Suppresses a Caspase-2 Apoptotic Response to DNA Damage that Bypasses p53, Bcl-2, and Caspase-3
Sidi, S., Sanda, T., Kennedy, R. D., Hagen, A. T., Jette, C. A., Hoffmans, R., Pascual, J., Imamura, S., Kishi, S., Amatruda, J. F., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.037 · Cited by 295 · see citing works
Ataxia Telangiectasia Mutated (ATM) Is Essential for DNA-PKcs Phosphorylations at the Thr-2609 Cluster upon DNA Double Strand Break
Chen, B. P. C., Uematsu, N., Kobayashi, J., Lerenthal, Y., Krempler, A., Yajima, H., Löbrich, M., Shiloh, Y., & Chen, D. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m611605200 · Cited by 296 · see citing works
Nuclear Acetyl-CoA Production by ACLY Promotes Homologous Recombination
Sivanand, S., Rhoades, S., Jiang, Q., Lee, J. V., Benci, J., Zhang, J., Yuan, S., Viney, I., Zhao, S., Carrer, A., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.008 · Cited by 295 · see citing works
Human BRCA1–BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection
Densham, R. M., Garvin, A. J., Stone, H. R., Strachan, J., Baldock, R. A., Daza-Martín, M., Fletcher, A., Blair-Reid, S., Beesley, J. F. J., Johal, B., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3236 · Cited by 283 · see citing works
Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism
Chen, P., Wu, J., Ding, C. C., Lin, C., Pan, S. M., Bossa, N., Xu, Y., Yang, W., Mathey-Prévôt, B., & Chi, J. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0393-7 · Cited by 288 · see citing works
A DNA-PKcs mutation in a radiosensitive T–B– SCID patient inhibits Artemis activation and nonhomologous end-joining
van der Burg, M., IJspeert, H., Verkaik, N. S., Turul, T., Wiegant, W. W., Morotomi‐Yano, K., Mari, P., Tezcan, İ., Chen, D. J., Zdzienicka, M. Z., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci37141 · Cited by 288 · see citing works
Involvement of novel autophosphorylation sites in ATM activation
Kozlov, S., Graham, M. E., Peng, C., Chen, P., Robinson, P. J., & Lavin, M. F. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601231 · Cited by 283 · see citing works
ATM-Dependent and -Independent Dynamics of the Nuclear Phosphoproteome After DNA Damage
Bensimon, A., Schmidt, A., Ziv, Y., Elkon, R., Wang, S., Chen, D. J., Aebersold, R. H., & Shiloh, Y. (2010) · Science Signaling · doi:10.1126/scisignal.2001034 · Cited by 275 · see citing works
Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise
Soleimani, R., Heytens, E., Darżynkiewicz, Z., & Oktay, K. (2011) · Aging · doi:10.18632/aging.100363 · Cited by 279 · see citing works
A new method for high-resolution imaging of Ku foci to decipher mechanisms of DNA double-strand break repair
Britton, S., Coates, J., & Jackson, S. P. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201303073 · Cited by 272 · see citing works
Self-citation
Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells
Neumaier, T., Swenson, J., Pham, C., Polyzos, A. A., Lo, A. T., Yang, P., Dyball, J., Asaithamby, A., Chen, D. J., Bissell, M. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117849108 · Cited by 266 · see citing works
Transient Inhibition of ATM Kinase Is Sufficient to Enhance Cellular Sensitivity to Ionizing Radiation
Rainey, M. D., Charlton, M. E., Stanton, R. V., & Kastan, M. B. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0763 · Cited by 267 · see citing works
NEMO and RIP1 Control Cell Fate in Response to Extensive DNA Damage via TNF-α Feedforward Signaling
Biton, S., & Ashkenazi, A. (2011) · Cell · doi:10.1016/j.cell.2011.02.023 · Cited by 262 · see citing works
Discovery of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3 Related (ATR) Protein Kinase as Potential Anticancer Agents
Charrier, J., Durrant, S. J., Golec, J. M. C., Kay, D. P., Knegtel, R. M. A., MacCormick, S., Mortimore, M., O'Donnell, M. E., Pinder, J. L., Reaper, P. M., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101488z · Cited by 256 · see citing works
Self-citation
Rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone ASF1
O’Sullivan, R. J., Arnoult, N., Lackner, D. H., Oganesian, L., Haggblom, C., Corpet, A., Almouzni, G., & Karlseder, J. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2754 · Cited by 259 · see citing works
DNA Damage Triggers Golgi Dispersal via DNA-PK and GOLPH3
Farber-Katz, S., Dippold, H. C., Buschman, M. D., Peterman, M. C., Xing, M., Noakes, C., Tat, J., Ng, M. M., Rahajeng, J., Cowan, D. M., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.023 · Cited by 257 · see citing works
BMI1 Is Recruited to DNA Breaks and Contributes to DNA Damage-Induced H2A Ubiquitination and Repair
Ginjala, V., Nacerddine, K., Kulkarni, A., Oza, J. H., Hill, S. J., Yao, M., Citterio, E., van Lohuizen, M., & Ganesan, S. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.00981-10 · Cited by 254 · see citing works
New Paradigms and Future Challenges in Radiation Oncology: An Update of Biological Targets and Technology
Liauw, S. L., Connell, P. P., & Weichselbaum, R. R. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005148 · Cited by 253 · see citing works
Morpholine as ubiquitous pharmacophore in medicinal chemistry: Deep insight into the structure-activity relationship (SAR)
Kumari, A., & Singh, R. K. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103578 · Cited by 253 · see citing works
Chromosome breakage after G2 checkpoint release
Deckbar, D., Birraux, J., Krempler, A., Tchouandong, L., Beucher, A., Walker, S., Stiff, T., Jeggo, P., & Löbrich, M. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612047 · Cited by 252 · see citing works
The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forksPreprint
Bansbach, C. E., Betous, R., Lovejoy, C. A., Glick, G. G., & Cortez, D. (2009) · Genes & Development · doi:10.1101/gad.1839909 · Cited by 249 · see citing works
Nucleoside analogs: molecular mechanisms signaling cell death
Ewald, B., Sampath, D., & Plunkett, W. K. (2008) · Oncogene · doi:10.1038/onc.2008.316 · Cited by 246 · see citing works
ATM in DNA repair in cancer
Jin, M. H., & Oh, D. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.07.002 · Cited by 246 · see citing works

Abstract 3928: KU-0060019, a novel small molecule inhibitor of ATM
Shea, K. F., Albertella, M. R., Bárdos, J. I., Batey, M. A., Cranston, A. N., Curtin, N. J., Griffin, R. J., Lau, A., Menear, K. A., Newell, D. R., et al. (2010) · Cancer Research · doi:10.1158/1538-7445.am10-3928
Self-citation
PRECLINICAL STUDIES ON ATM KINASE INHIBITORS AS ANTI-CANCER AGENTS
Choi, S. (2011) · D-Scholarship@Pitt (University of Pittsburgh)
Transient Inhibition of ATM Kinase Is Sufficient to Enhance Cellular Sensitivity to Ionizing Radiation
Rainey, M. D., Charlton, M. E., Stanton, R. V., & Kastan, M. B. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0763 · Cited by 267 · see citing works
Pharmacological inhibition of ATM by KU55933 stimulates ATM transcription
Khalil, H. S., Tummala, H., Hupp, T. R., & Zhelev, N. (2012) · Experimental Biology and Medicine · doi:10.1258/ebm.2012.011378 · Cited by 24 · see citing works
Irreversible chromosome damage accumulates rapidly in the absence of ATM kinase activity
White, J. S., Choi, S., & Bakkenist, C. J. (2008) · Cell Cycle · doi:10.4161/cc.7.9.5961 · Cited by 51 · see citing works

Authors: 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.
Affiliations: 1KuDOS Pharmaceuticals Ltd., Cambridge Science Park, Milton Road, Cambridge;
Newcastle University (GB)
University of Cambridge (GB)
ORCID: Hickson, Ian
Zhao, Yan
Martin, Niall M. B.
Jackson, Stephen P.
Curtin, Nicola J.
Smith, Graeme C. M.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2004-12-15
Volume: 64
Issue: 24
Pages: 9152-9159
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-04-2727
OpenAlex: W2101988823
Cited by: 1,220
References: 58
Citations by year: 2026: 26 · 2025: 31 · 2024: 38 · 2023: 49 · 2022: 31 · 2021: 32 · 2020: 53 · 2019: 55 · 2018: 48 · 2017: 66 · 2016: 71 · 2015: 76 · 2014: 70 · 2013: 62 · 2012: 92
FWCI: 11.39
Type: journal article
Language: en
Open access: green
doi.org
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
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 kinase, KU55933, kinase inhibitors, ataxia telangiectasia, radiosensitivity, DNA double-strand breaks, cell cycle arrest, p53 phosphorylation, NBS1, radiosensitization, chemosensitization, etoposide, doxorubicin, camptothecin, γH2AX, SMC1A
MeSH terms: Cell Cycle, Chromones, DNA-Binding Proteins, HeLa Cells, Humans, Kinetics, Morpholines, Phosphorylation, Pyrones, Radiation-Sensitizing Agents, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Inhibitory Concentration 50, Combinatorial Chemistry Techniques, Tumor Suppressor Proteins, Cell Line, Tumor, Protein Kinase Inhibitors, Ataxia Telangiectasia Mutated Proteins

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Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM

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