Skip Navigation


Carcinogenesis Advance Access originally published online on August 14, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
24/10/1571    most recent
bgg137v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (79)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yang, J.
Right arrow Articles by Duerksen-Hughes, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, J.
Right arrow Articles by Duerksen-Hughes, P. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol. 24, No. 10, 1571-1580, October 2003
© 2003 Oxford University Press

REVIEW

ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses

Jun Yang1,2, Yingnian Yu1,2, Hope E. Hamrick3 and Penelope J. Duerksen-Hughes4,5

1 Department of Pathology and Pathophysiology and 2 Department of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310031, China, 3 Department of Psychology, Wellesley College, Wellesley, MA 02481, USA and 4 Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA

Exposure to genotoxic agents is a major cause of human cancer, and cellular responses to genotoxic stress are important defense mechanisms. These responses are very complex, involving many cellular factors that form an extensive signal transduction network. This network includes a protein kinase cascade that connects the detection of DNA damage to the activation of transcription factors, which in turn regulate the expression of genes involved in DNA repair, cell cycle arrest and programmed cell death (apoptosis). The mitogen-activated protein kinases are the best-studied members of the kinase cascade with an acknowledged role in the genotoxic stress response. However, the initial activation of the protein kinase cascade is not fully understood, although several protein kinases, such as ataxia telangiectasia, mutated (ATM), ATM- and Rad3-related (ATR), and DNA-dependent protein kinase (DNA-PK) in humans, are increasingly recognized for their potential roles in the sensing of DNA damage and initiating the subsequent protein kinase cascade. In this review, the properties of these three kinases are discussed and their functions in the initiation of the genotoxic stress response are explored.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
N. Pabla, S. Huang, Q.-S. Mi, R. Daniel, and Z. Dong
ATR-Chk2 Signaling in p53 Activation and DNA Damage Response during Cisplatin-induced Apoptosis
J. Biol. Chem., March 7, 2008; 283(10): 6572 - 6583.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Wang, Y. Zhao, L. Li, M. A. McNutt, L. Wu, S. Lu, Y. Yu, W. Zhou, J. Feng, G. Chai, et al.
An ATM- and Rad3-related (ATR) Signaling Pathway and a Phosphorylation-Acetylation Cascade Are Involved in Activation of p53/p21Waf1/Cip1 in Response to 5-Aza-2'-deoxycytidine Treatment
J. Biol. Chem., February 1, 2008; 283(5): 2564 - 2574.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. Gao, L. A. Mitchell, F. T. Lauer, and S. W. Burchiel
p53 and ATM/ATR Regulate 7,12-Dimethylbenz[a]anthracene-Induced Immunosuppression
Mol. Pharmacol., January 1, 2008; 73(1): 137 - 146.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Herman-Antosiewicz, H. Xiao, K. L. Lew, and S. V. Singh
Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line
Mol. Cancer Ther., May 1, 2007; 6(5): 1673 - 1681.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Herman-Antosiewicz, S. D. Stan, E.-R. Hahm, D. Xiao, and S. V. Singh
Activation of a novel ataxia-telangiectasia mutated and Rad3 related/checkpoint kinase 1-dependent prometaphase checkpoint in cancer cells by diallyl trisulfide, a promising cancer chemopreventive constituent of processed garlic
Mol. Cancer Ther., April 1, 2007; 6(4): 1249 - 1261.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. Choi, K. L. Lew, H. Xiao, A. Herman-Antosiewicz, D. Xiao, C. K. Brown, and S. V. Singh
D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1
Carcinogenesis, January 1, 2007; 28(1): 151 - 162.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Z. Dong and A. E. Tomkinson
ATM mediates oxidative stress-induced dephosphorylation of DNA ligase III{alpha}
Nucleic Acids Res., November 6, 2006; 34(20): 5721 - 5279.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
I. Malavazi, M. Savoldi, S. M. Z. Di Mauro, C. F. M. Menck, S. D. Harris, M. H. d. S. Goldman, and G. H. Goldman
Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage.
Eukaryot. Cell, October 1, 2006; 5(10): 1688 - 1704.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
R. P Singh and R. Agarwal
Mechanisms of action of novel agents for prostate cancer chemoprevention.
Endocr. Relat. Cancer, September 1, 2006; 13(3): 751 - 778.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B.-J. Park, Y. S. Oh, S. Y. Park, S. J. Choi, C. Rudolph, B. Schlegelberger, and S. Kim
AIMP3 Haploinsufficiency Disrupts Oncogene-Induced p53 Activation and Genomic Stability.
Cancer Res., July 15, 2006; 66(14): 6913 - 6918.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
M. D. Maloney, J. J. Goater, R. Parsons, H. Ito, R. J. O'Keefe, P. T. Rubery, M. H. Drissi, and E. M. Schwarz
Safety and Efficacy of Ultraviolet-A Light-Activated Gene Transduction for Gene Therapy of Articular Cartilage Defects
J. Bone Joint Surg. Am., April 1, 2006; 88(4): 753 - 761.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
M. G. Hovest, N. Bruggenolte, K. S. Hosseini, T. Krieg, and G. Herrmann
Senescence of Human Fibroblasts after Psoralen Photoactivation Is Mediated by ATR Kinase and Persistent DNA Damage Foci at Telomeres
Mol. Biol. Cell, April 1, 2006; 17(4): 1758 - 1767.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Nubel, J. Damrot, W. P. Roos, B. Kaina, and G. Fritz
Lovastatin Protects Human Endothelial Cells from Killing by Ionizing Radiation without Impairing Induction and Repair of DNA Double-Strand Breaks
Clin. Cancer Res., February 1, 2006; 12(3): 933 - 939.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Hu, M. E. Mancl, and B. J. Barnes
Signaling through IFN Regulatory Factor-5 Sensitizes p53-Deficient Tumors to DNA Damage-Induced Apoptosis and Cell Death
Cancer Res., August 15, 2005; 65(16): 7403 - 7412.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Herman-Antosiewicz and S. V. Singh
Checkpoint Kinase 1 Regulates Diallyl Trisulfide-induced Mitotic Arrest in Human Prostate Cancer Cells
J. Biol. Chem., August 5, 2005; 280(31): 28519 - 28528.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
M. R. v. Z. K. Fagundes, C. P. Semighini, I. Malavazi, M. Savoldi, J. F. de Lima, M. H. de Souza Goldman, S. D. Harris, and G. H. Goldman
Aspergillus nidulans uvsBATR and scaANBS1 Genes Show Genetic Interactions during Recovery from Replication Stress and DNA Damage
Eukaryot. Cell, July 1, 2005; 4(7): 1239 - 1252.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Dhanalakshmi, C. Agarwal, R. P. Singh, and R. Agarwal
Silibinin Up-regulates DNA-Protein Kinase-dependent p53 Activation to Enhance UVB-induced Apoptosis in Mouse Epithelial JB6 Cells
J. Biol. Chem., May 27, 2005; 280(21): 20375 - 20383.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. V. Singh, S. K. Srivastava, S. Choi, K. L. Lew, J. Antosiewicz, D. Xiao, Y. Zeng, S. C. Watkins, C. S. Johnson, D. L. Trump, et al.
Sulforaphane-induced Cell Death in Human Prostate Cancer Cells Is Initiated by Reactive Oxygen Species
J. Biol. Chem., May 20, 2005; 280(20): 19911 - 19924.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
H. J. Boeckman, K. S. Trego, and J. J. Turchi
Cisplatin Sensitizes Cancer Cells to Ionizing Radiation via Inhibition of Nonhomologous End Joining
Mol. Cancer Res., May 1, 2005; 3(5): 277 - 285.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. D. West, C. Ji, and L. J. Marnett
Modulation of DNA Fragmentation Factor 40 Nuclease Activity by Poly(ADP-ribose) Polymerase-1
J. Biol. Chem., April 15, 2005; 280(15): 15141 - 15147.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
L. M. Karnitz and S. J. H. Arlander
Chk1, a Novel Target to Sensitize Tumor Cells to Replication Inhibitors
Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 254 - 257.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Li and D. F. Stern
Regulation of CHK2 by DNA-dependent Protein Kinase
J. Biol. Chem., March 25, 2005; 280(12): 12041 - 12050.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. L. DeHart, J. L. Andersen, E. S. Zimmerman, O. Ardon, D. S. An, J. Blackett, B. Kim, and V. Planelles
The Ataxia Telangiectasia-Mutated and Rad3-Related Protein Is Dispensable for Retroviral Integration
J. Virol., February 1, 2005; 79(3): 1389 - 1396.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. S. Pawelczak, B. J. Andrews, and J. J. Turchi
Differential activation of DNA-PK based on DNA strand orientation and sequence bias
Nucleic Acids Res., January 7, 2005; 33(1): 152 - 161.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
T. D. McSherry and P. R. Mueller
Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends
Mol. Cell. Biol., November 15, 2004; 24(22): 9968 - 9985.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
M. R. V. Z. K. Fagundes, J. F. Lima, M. Savoldi, I. Malavazi, R. E. Larson, M. H. S. Goldman, and G. H. Goldman
The Aspergillus nidulans npkA Gene Encodes a Cdc2-Related Kinase That Genetically Interacts With the UvsBATR Kinase
Genetics, August 1, 2004; 167(4): 1629 - 1641.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. V. Singh, A. Herman-Antosiewicz, A. V. Singh, K. L. Lew, S. K. Srivastava, R. Kamath, K. D. Brown, L. Zhang, and R. Baskaran
Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C
J. Biol. Chem., June 11, 2004; 279(24): 25813 - 25822.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
K. D. Mills, D. O. Ferguson, J. Essers, M. Eckersdorff, R. Kanaar, and F. W. Alt
Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability
Genes & Dev., June 1, 2004; 18(11): 1283 - 1292.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.