Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 288 (5470): 1425-1429

Copyright © 2000 by the American Association for the Advancement of Science

Rapid Destruction of Human Cdc25A in Response to DNA Damage

Niels Mailand, Jacob Falck, Claudia Lukas, Randi G. Syljuåsen, Markus Welcker, Jiri Bartek, * Jiri Lukas

To protect genome integrity and ensure survival, eukaryotic cells exposed to genotoxic stress cease proliferating to provide time for DNA repair. Human cells responded to ultraviolet light or ionizing radiation by rapid, ubiquitin- and proteasome-dependent protein degradation of Cdc25A, a phosphatase that is required for progression from G1 to S phase of the cell cycle. This response involved activated Chk1 protein kinase but not the p53 pathway, and the persisting inhibitory tyrosine phosphorylation of Cdk2 blocked entry into S phase and DNA replication. Overexpression of Cdc25A bypassed this mechanism, leading to enhanced DNA damage and decreased cell survival. These results identify specific degradation of Cdc25A as part of the DNA damage checkpoint mechanism and suggest how Cdc25A overexpression in human cancers might contribute to tumorigenesis.

Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
*   To whom correspondence should be addressed. E-mail: bartek{at}biobase.dk


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
S-adenosylmethionine limitation induces p38 mitogen-activated protein kinase and triggers cell cycle arrest in G1.
D.-W. Lin, B. P. Chung, and P. Kaiser (2014)
J. Cell Sci. 127, 50-59
   Abstract »    Full Text »    PDF »
Ei24, a Novel E2F Target Gene, Affects p53-independent Cell Death upon Ultraviolet C Irradiation.
Y. H. Sung, Y. Jin, Y. Kang, S. Devkota, J. Lee, J.-i. Roh, and H.-W. Lee (2013)
J. Biol. Chem. 288, 31261-31267
   Abstract »    Full Text »    PDF »
Degradation of p12 Subunit by CRL4Cdt2 E3 Ligase Inhibits Fork Progression after DNA Damage.
K. Terai, E. Shibata, T. Abbas, and A. Dutta (2013)
J. Biol. Chem. 288, 30509-30514
   Abstract »    Full Text »    PDF »
Phosphorylation-triggered CUEDC2 degradation promotes UV-induced G1 arrest through APC/CCdh1 regulation.
W.-N. Zhang, J. Zhou, T. Zhou, A.-L. Li, N. Wang, J.-J. Xu, Y. Chang, J.-H. Man, X. Pan, T. Li, et al. (2013)
PNAS 110, 11017-11022
   Abstract »    Full Text »    PDF »
Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint.
P. Kleiblova, I. A. Shaltiel, J. Benada, J. evcik, S. Pechackova, P. Pohlreich, E. E. Voest, P. Dundr, J. Bartek, Z. Kleibl, et al. (2013)
J. Cell Biol. 201, 511-521
   Abstract »    Full Text »    PDF »
UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway.
D. O. Warmerdam, E. K. Brinkman, J. A. Marteijn, R. H. Medema, R. Kanaar, and V. A. J. Smits (2013)
J. Cell Sci. 126, 1923-1930
   Abstract »    Full Text »    PDF »
SMC1-Mediated Intra-S-Phase Arrest Facilitates Bocavirus DNA Replication.
Y. Luo, X. Deng, F. Cheng, Y. Li, and J. Qiu (2013)
J. Virol. 87, 4017-4032
   Abstract »    Full Text »    PDF »
Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates.
K. J. Neelsen, I. M. Y. Zanini, R. Herrador, and M. Lopes (2013)
J. Cell Biol. 200, 699-708
   Abstract »    Full Text »    PDF »
CDK targeting of NBS1 promotes DNA-end resection, replication restart and homologous recombination.
J. Falck, J. V. Forment, J. Coates, M. Mistrik, J. Lukas, J. Bartek, and S. P. Jackson (2012)
EMBO Rep. 13, 561-568
   Abstract »    Full Text »    PDF »
Chk1 phosphorylates the tumour suppressor Mig-6, regulating the activation of EGF signalling.
N. Liu, M. Matsumoto, K. Kitagawa, Y. Kotake, S. Suzuki, S. Shirasawa, K. I. Nakayama, M. Nakanishi, H. Niida, and M. Kitagawa (2012)
EMBO J. 31, 2365-2377
   Abstract »    Full Text »    PDF »
Loss of Cyclin-Dependent Kinase 2 (CDK2) Inhibitory Phosphorylation in a CDK2AF Knock-In Mouse Causes Misregulation of DNA Replication and Centrosome Duplication.
H. Zhao, X. Chen, M. Gurian-West, and J. M. Roberts (2012)
Mol. Cell. Biol. 32, 1421-1432
   Abstract »    Full Text »    PDF »
GO-function: deriving biologically relevant functions from statistically significant functions.
J. Wang, X. Zhou, J. Zhu, Y. Gu, W. Zhao, J. Zou, and Z. Guo (2012)
Brief Bioinform 13, 216-227
   Abstract »    Full Text »    PDF »
Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints.
N. Pabla, K. Bhatt, and Z. Dong (2012)
PNAS 109, 197-202
   Abstract »    Full Text »    PDF »
Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease.
R. Dominguez-Kelly, Y. Martin, S. Koundrioukoff, M. E. Tanenbaum, V. A. J. Smits, R. H. Medema, M. Debatisse, and R. Freire (2011)
J. Cell Biol. 194, 567-579
   Abstract »    Full Text »    PDF »
Hsp90 Inhibitor-Mediated Disruption of Chaperone Association of ATR with Hsp90 Sensitizes Cancer Cells to DNA Damage.
K. Ha, W. Fiskus, R. Rao, R. Balusu, S. Venkannagari, N. R. Nalabothula, and K. N. Bhalla (2011)
Mol. Cancer Ther. 10, 1194-1206
   Abstract »    Full Text »    PDF »
Human Cdc14A Phosphatase Modulates the G2/M Transition through Cdc25A and Cdc25B.
M. D. Vazquez-Novelle, N. Mailand, S. Ovejero, A. Bueno, and M. P. Sacristan (2010)
J. Biol. Chem. 285, 40544-40553
   Abstract »    Full Text »    PDF »
The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage.
D. H. Larsen, C. Poinsignon, T. Gudjonsson, C. Dinant, M. R. Payne, F. J. Hari, J. M. Rendtlew Danielsen, P. Menard, J. C. Sand, M. Stucki, et al. (2010)
J. Cell Biol. 190, 731-740
   Abstract »    Full Text »    PDF »
14-3-3{gamma} mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage.
K. Kasahara, H. Goto, M. Enomoto, Y. Tomono, T. Kiyono, and M. Inagaki (2010)
EMBO J. 29, 2802-2812
   Abstract »    Full Text »    PDF »
A Novel Mechanism of Indole-3-Carbinol Effects on Breast Carcinogenesis Involves Induction of Cdc25A Degradation.
Y. Wu, X. Feng, Y. Jin, Z. Wu, W. Hankey, C. Paisie, L. Li, F. Liu, S. H. Barsky, W. Zhang, et al. (2010)
Cancer Prevention Research 3, 818-828
   Abstract »    Full Text »    PDF »
MiR-322/424 and -503 Are Induced during Muscle Differentiation and Promote Cell Cycle Quiescence and Differentiation by Down-Regulation of Cdc25A.
S. Sarkar, B. K. Dey, and A. Dutta (2010)
Mol. Biol. Cell 21, 2138-2149
   Abstract »    Full Text »    PDF »
Mechanism of Radiosensitization by the Chk1/2 Inhibitor AZD7762 Involves Abrogation of the G2 Checkpoint and Inhibition of Homologous Recombinational DNA Repair.
M. A. Morgan, L. A. Parsels, L. Zhao, J. D. Parsels, M. A. Davis, M. C. Hassan, S. Arumugarajah, L. Hylander-Gans, D. Morosini, D. M. Simeone, et al. (2010)
Cancer Res. 70, 4972-4981
   Abstract »    Full Text »    PDF »
The Limitations of the G1-S Checkpoint.
D. Deckbar, T. Stiff, B. Koch, C. Reis, M. Lobrich, and P. A. Jeggo (2010)
Cancer Res. 70, 4412-4421
   Abstract »    Full Text »    PDF »
Cdc25 Phosphatases Are Required for Timely Assembly of CDK1-Cyclin B at the G2/M Transition.
O. Timofeev, O. Cizmecioglu, F. Settele, T. Kempf, and I. Hoffmann (2010)
J. Biol. Chem. 285, 16978-16990
   Abstract »    Full Text »    PDF »
ATR/Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells.
E. Despras, F. Daboussi, O. Hyrien, K. Marheineke, and P. L. Kannouche (2010)
Hum. Mol. Genet. 19, 1690-1701
   Abstract »    Full Text »    PDF »
Overall Cdk activity modulates the DNA damage response in mammalian cells.
A. Cerqueira, D. Santamaria, B. Martinez-Pastor, M. Cuadrado, O. Fernandez-Capetillo, and M. Barbacid (2009)
J. Cell Biol. 187, 773-780
   Abstract »    Full Text »    PDF »
MAPK Pathway Activation Delays G2/M Progression by Destabilizing Cdc25B.
P. Astuti, T. Pike, C. Widberg, E. Payne, A. Harding, J. Hancock, and B. Gabrielli (2009)
J. Biol. Chem. 284, 33781-33788
   Abstract »    Full Text »    PDF »
Mice with the CHEK2*1100delC SNP are predisposed to cancer with a strong gender bias.
E. M. Bahassi, S. B. Robbins, M. Yin, G. P. Boivin, R. Kuiper, H. van Steeg, and P. J. Stambrook (2009)
PNAS 106, 17111-17116
   Abstract »    Full Text »    PDF »
Prevalence and Functional Analysis of Sequence Variants in the ATR Checkpoint Mediator Claspin.
J. Zhang, Y.-H. Song, B. W. Brannigan, D. C.R. Wahrer, T. A. Schiripo, P. L. Harris, S. M. Haserlat, L. E. Ulkus, K. M. Shannon, J. E. Garber, et al. (2009)
Mol. Cancer Res. 7, 1510-1516
   Abstract »    Full Text »    PDF »
MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response.
J. Pothof, N. S. Verkaik, W. van IJcken, E. A. C. Wiemer, V. T. B. Ta, G. T. J. van der Horst, N. G. J. Jaspers, D. C. van Gent, J. H. J. Hoeijmakers, and S. P. Persengiev (2009)
EMBO J. 28, 2090-2099
   Abstract »    Full Text »    PDF »
Short 42{degrees}C heat shock induces phosphorylation and degradation of Cdc25A which depends on p38MAPK, Chk2 and 14.3.3.
S. Madlener, M. Rosner, S. Krieger, B. Giessrigl, M. Gridling, T. P. N. Vo, C. Leisser, A. Lackner, I. Raab, M. Grusch, et al. (2009)
Hum. Mol. Genet. 18, 1990-2000
   Abstract »    Full Text »    PDF »
The Extracellular Signal-regulated Kinase-Mitogen-activated Protein Kinase Pathway Phosphorylates and Targets Cdc25A for SCF{beta}-TrCP-dependent Degradation for Cell Cycle Arrest.
M. Isoda, Y. Kanemori, N. Nakajo, S. Uchida, K. Yamashita, H. Ueno, and N. Sagata (2009)
Mol. Biol. Cell 20, 2186-2195
   Abstract »    Full Text »    PDF »
Checkpoint-Dependent Regulation of Origin Firing and Replication Fork Movement in Response to DNA Damage in Fission Yeast.
S. Kumar and J. A. Huberman (2009)
Mol. Cell. Biol. 29, 602-611
   Abstract »    Full Text »    PDF »
USP7 counteracts SCF{beta}TrCP- but not APCCdh1-mediated proteolysis of Claspin.
H. Faustrup, S. Bekker-Jensen, J. Bartek, J. Lukas, and N. Mailand (2009)
J. Cell Biol. 184, 13-19
   Abstract »    Full Text »    PDF »
90-kDa Heat Shock Protein Inhibition Abrogates the Topoisomerase I Poison-Induced G2/M Checkpoint in p53-Null Tumor Cells by Depleting Chk1 and Wee1.
A. N. Tse, T. N. Sheikh, H. Alan, T.-C. Chou, and G. K. Schwartz (2009)
Mol. Pharmacol. 75, 124-133
   Abstract »    Full Text »    PDF »
Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control.
D. Wilsker, E. Petermann, T. Helleday, and F. Bunz (2008)
PNAS 105, 20752-20757
   Abstract »    Full Text »    PDF »
Cdc25A Serine 123 Phosphorylation Couples Centrosome Duplication with DNA Replication and Regulates Tumorigenesis.
S. Shreeram, W. K. Hee, and D. V. Bulavin (2008)
Mol. Cell. Biol. 28, 7442-7450
   Abstract »    Full Text »    PDF »
Improving Gemcitabine-Mediated Radiosensitization Using Molecularly Targeted Therapy: A Review.
M. A. Morgan, L. A. Parsels, J. Maybaum, and T. S. Lawrence (2008)
Clin. Cancer Res. 14, 6744-6750
   Abstract »    Full Text »    PDF »
Aberrant Polo-Like Kinase 1-Cdc25A Pathway in Metastatic Hepatocellular Carcinoma.
X. Q. Wang, Y. Q. Zhu, K. S. Lui, Q. Cai, P. Lu, and R. T. Poon (2008)
Clin. Cancer Res. 14, 6813-6820
   Abstract »    Full Text »    PDF »
Multimodal Control of Cdc25A by Nitrosative Stress.
R. J. Tomko Jr. and J. S. Lazo (2008)
Cancer Res. 68, 7457-7465
   Abstract »    Full Text »    PDF »
AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies.
S. D. Zabludoff, C. Deng, M. R. Grondine, A. M. Sheehy, S. Ashwell, B. L. Caleb, S. Green, H. R. Haye, C. L. Horn, J. W. Janetka, et al. (2008)
Mol. Cancer Ther. 7, 2955-2966
   Abstract »    Full Text »    PDF »
Differential Roles for Checkpoint Kinases in DNA Damage-dependent Degradation of the Cdc25A Protein Phosphatase.
J. Jin, X. L. Ang, X. Ye, M. Livingstone, and J. W. Harper (2008)
J. Biol. Chem. 283, 19322-19328
   Abstract »    Full Text »    PDF »
DNA Damage Detection and Repair Pathways--Recent Advances with Inhibitors of Checkpoint Kinases in Cancer Therapy.
S. Ashwell and S. Zabludoff (2008)
Clin. Cancer Res. 14, 4032-4037
   Abstract »    Full Text »    PDF »
Cdc6 Determines Utilization of p21WAF1/CIP1-dependent Damage Checkpoint in S Phase Cells.
Q. Kan, S. Jinno, K. Kobayashi, H. Yamamoto, and H. Okayama (2008)
J. Biol. Chem. 283, 17864-17872
   Abstract »    Full Text »    PDF »
Overexpression of CDC25B and LAMC2 mRNA and Protein in Esophageal Squamous Cell Carcinomas and Premalignant Lesions in Subjects from a High-Risk Population in China.
J.-Z. Shou, N. Hu, M. Takikita, M. J. Roth, L. L. Johnson, C. Giffen, Q.-H. Wang, C. Wang, Y. Wang, H. Su, et al. (2008)
Cancer Epidemiol. Biomarkers Prev. 17, 1424-1435
   Abstract »    Full Text »    PDF »
Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins.
M. Huang, Z.-H. Miao, H. Zhu, Y.-J. Cai, W. Lu, and J. Ding (2008)
Mol. Cancer Ther. 7, 1440-1449
   Abstract »    Full Text »    PDF »
Profiling of UV-induced ATM/ATR signaling pathways.
M. P. Stokes, J. Rush, J. MacNeill, J. M. Ren, K. Sprott, J. Nardone, V. Yang, S. A. Beausoleil, S. P. Gygi, M. Livingstone, et al. (2007)
PNAS 104, 19855-19860
   Abstract »    Full Text »    PDF »
Cell Division Cycle 25B Phosphatase Is Essential for Benzo(a)Pyrene-7,8-Diol-9,10-Epoxide Induced Neoplastic Transformation.
S. K. Srivastava, P. Bansal, T. Oguri, J. S. Lazo, and S. V. Singh (2007)
Cancer Res. 67, 9150-9157
   Abstract »    Full Text »    PDF »
In Non-neoplastic Barrett's Epithelial Cells, Acid Exerts Early Antiproliferative Effects through Activation of the Chk2 Pathway.
H.-Y. Zhang, X. Zhang, K. Hormi-Carver, L. A. Feagins, S. J. Spechler, and R. F. Souza (2007)
Cancer Res. 67, 8580-8587
   Abstract »    Full Text »    PDF »
Hemizygous Disruption of Cdc25A Inhibits Cellular Transformation and Mammary Tumorigenesis in Mice.
D. Ray, Y. Terao, D. Nimbalkar, H. Hirai, E. C. Osmundson, X. Zou, R. Franks, K. Christov, and H. Kiyokawa (2007)
Cancer Res. 67, 6605-6611
   Abstract »    Full Text »    PDF »
A Proteomic Analysis of Ataxia Telangiectasia-mutated (ATM)/ATM-Rad3-related (ATR) Substrates Identifies the Ubiquitin-Proteasome System as a Regulator for DNA Damage Checkpoints.
J.-J. Mu, Y. Wang, H. Luo, M. Leng, J. Zhang, T. Yang, D. Besusso, S. Y. Jung, and J. Qin (2007)
J. Biol. Chem. 282, 17330-17334
   Abstract »    Full Text »    PDF »
Human TopBP1 Participates in Cyclin E/CDK2 Activation and Preinitiation Complex Assembly during G1/S Transition.
Y. Jeon, K. Y. Lee, M. J. Ko, Y. S. Lee, S. Kang, and D. S. Hwang (2007)
J. Biol. Chem. 282, 14882-14890
   Abstract »    Full Text »    PDF »
Human prostate epithelium lacks Wee1A-mediated DNA damage-induced checkpoint enforcement.
T. M. Kiviharju-af Hallstrom, S. Jaamaa, M. Monkkonen, K. Peltonen, L. C. Andersson, R. H. Medema, D. M. Peehl, and M. Laiho (2007)
PNAS 104, 7211-7216
   Abstract »    Full Text »    PDF »
Chk1-Mediated Phosphorylation of FANCE Is Required for the Fanconi Anemia/BRCA Pathway.
X. Wang, R. D. Kennedy, K. Ray, P. Stuckert, T. Ellenberger, and A. D. D'Andrea (2007)
Mol. Cell. Biol. 27, 3098-3108
   Abstract »    Full Text »    PDF »
Induction of Cdc25B Regulates Cell Cycle Resumption after Genotoxic Stress.
P. Bansal and J. S. Lazo (2007)
Cancer Res. 67, 3356-3363
   Abstract »    Full Text »    PDF »
Targeting Checkpoint Kinase 1 in Cancer Therapeutics.
A. N. Tse, R. Carvajal, and G. K. Schwartz (2007)
Clin. Cancer Res. 13, 1955-1960
   Abstract »    Full Text »    PDF »
Cdc7-Dbf4 and the Human S Checkpoint Response to UVC.
T. P. Heffernan, K. Unsal-Kacmaz, A. N. Heinloth, D. A. Simpson, R. S. Paules, A. Sancar, M. Cordeiro-Stone, and W. K. Kaufmann (2007)
J. Biol. Chem. 282, 9458-9468
   Abstract »    Full Text »    PDF »
How Tyrosine 15 Phosphorylation Inhibits the Activity of Cyclin-dependent Kinase 2-Cyclin A.
J. P. I. Welburn, J. A. Tucker, T. Johnson, L. Lindert, M. Morgan, A. Willis, M. E. M. Noble, and J. A. Endicott (2007)
J. Biol. Chem. 282, 3173-3181
   Abstract »    Full Text »    PDF »
HIV Protease Inhibitor Nelfinavir Inhibits Growth of Human Melanoma Cells by Induction of Cell Cycle Arrest.
W. Jiang, P. J. Mikochik, J. H. Ra, H. Lei, K. T. Flaherty, J. D. Winkler, and F. R. Spitz (2007)
Cancer Res. 67, 1221-1227
   Abstract »    Full Text »    PDF »
CHIR-124, a Novel Potent Inhibitor of Chk1, Potentiates the Cytotoxicity of Topoisomerase I Poisons In vitro and In vivo.
A. N. Tse, K. G. Rendahl, T. Sheikh, H. Cheema, K. Aardalen, M. Embry, S. Ma, E. J. Moler, Z. J. Ni, D. E. Lopes de Menezes, et al. (2007)
Clin. Cancer Res. 13, 591-602
   Abstract »    Full Text »    PDF »
p53-based cancer therapies: is defective p53 the Achilles heel of the tumor?.
A. A. Levesque and A. Eastman (2007)
Carcinogenesis 28, 13-20
   Abstract »    Full Text »    PDF »
Cell signalling mechanisms and the control of cell life and death.
O. Sapora and B. Di Carlo (2006)
Radiat Prot Dosimetry 122, 210-220
   Full Text »    PDF »
CDK2-Dependent Phosphorylation of FOXO1 as an Apoptotic Response to DNA Damage.
H. Huang, K. M. Regan, Z. Lou, J. Chen, and D. J. Tindall (2006)
Science 314, 294-297
   Abstract »    Full Text »    PDF »
The Chk1-mediated S-phase Checkpoint Targets Initiation Factor Cdc45 via a Cdc25A/Cdk2-independent Mechanism.
P. Liu, L. R. Barkley, T. Day, X. Bi, D. M. Slater, M. G. Alexandrow, H.-P. Nasheuer, and C. Vaziri (2006)
J. Biol. Chem. 281, 30631-30644
   Abstract »    Full Text »    PDF »
Development of a Screening Assay for Surrogate Markers of Chk1 Inhibitor-Induced Cell Cycle Release.
C. P. Fanton, M. W. Rowe, E. J. Moler, M. Ison-Dugenny, S. K. De Long, K. Rendahl, Y. Shao, T. Slabiak, T. G. Gesner, and M. L. MacKichan (2006)
J Biomol Screen 11, 792-806
   Abstract »    PDF »
Chk1- and Claspin-Dependent but ATR/ATM- and Rad17-Independent DNA Replication Checkpoint Response in HeLa Cells..
V. Rodriguez-Bravo, S. Guaita-Esteruelas, R. Florensa, O. Bachs, and N. Agell (2006)
Cancer Res. 66, 8672-8679
   Abstract »    Full Text »    PDF »
Identification of Cell Cycle Regulatory Genes as Principal Targets of p53-mediated Transcriptional Repression.
K. B. Spurgers, D. L. Gold, K. R. Coombes, N. L. Bohnenstiehl, B. Mullins, R. E. Meyn, C. J. Logothetis, and T. J. McDonnell (2006)
J. Biol. Chem. 281, 25134-25142
   Abstract »    Full Text »    PDF »
The Chk1/Cdc25A Pathway as Activators of the Cell Cycle in Neuronal Death Induced by Camptothecin..
Y. Zhang, D. Qu, E. J. Morris, M. J. O'Hare, S. M. Callaghan, R. S. Slack, H. M. Geller, and D. S. Park (2006)
J. Neurosci. 26, 8819-8828
   Abstract »    Full Text »    PDF »
Claspin Operates Downstream of TopBP1 To Direct ATR Signaling towards Chk1 Activation.
S. Liu, S. Bekker-Jensen, N. Mailand, C. Lukas, J. Bartek, and J. Lukas (2006)
Mol. Cell. Biol. 26, 6056-6064
   Abstract »    Full Text »    PDF »
Constitutive and UV-induced Fibronectin Degradation Is a Ubiquitination-dependent Process Controlled by beta-TrCP.
D. Ray, E. C. Osmundson, and H. Kiyokawa (2006)
J. Biol. Chem. 281, 23060-23065
   Abstract »    Full Text »    PDF »
Checkpoint proteins control survival of the postmitotic cells in Caenorhabditis elegans..
A. Olsen, M. C. Vantipalli, and G. J. Lithgow (2006)
Science 312, 1381-1385
   Abstract »    Full Text »    PDF »
DNA damage responses and their many interactions with the replication fork.
P. R. Andreassen, G. P. H. Ho, and A. D. D'Andrea (2006)
Carcinogenesis 27, 883-892
   Abstract »    Full Text »    PDF »
DNA Damage during Reoxygenation Elicits a Chk2-Dependent Checkpoint Response.
R. A. Freiberg, E. M. Hammond, M. J. Dorie, S. M. Welford, and A. J. Giaccia (2006)
Mol. Cell. Biol. 26, 1598-1609
   Abstract »    Full Text »    PDF »
Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins.
M. Gaspar and T. Shenk (2006)
PNAS 103, 2821-2826
   Abstract »    Full Text »    PDF »
Hzf, a p53-Responsive Gene, Regulates Maintenance of the G2 Phase Checkpoint Induced by DNA Damage.
M. Sugimoto, A. Gromley, and C. J. Sherr (2006)
Mol. Cell. Biol. 26, 502-512
   Abstract »    Full Text »    PDF »
DNA damage checkpoints in mammals.
H. Niida and M. Nakanishi (2006)
Mutagenesis 21, 3-9
   Abstract »    Full Text »    PDF »
Ataxia-telangiectasia-mutated (ATM) Is a T-antigen Kinase That Controls SV40 Viral Replication in Vivo.
Y. Shi, G. E. Dodson, S. Shaikh, K. Rundell, and R. S. Tibbetts (2005)
J. Biol. Chem. 280, 40195-40200
   Abstract »    Full Text »    PDF »
Proliferating Cell Nuclear Antigen Recruits Cyclin-dependent Kinase Inhibitor Xic1 to DNA and Couples Its Proteolysis to DNA Polymerase Switching.
L.-C. Chuang and P. R. Yew (2005)
J. Biol. Chem. 280, 35299-35309
   Abstract »    Full Text »    PDF »
How adeno-associated virus Rep78 protein arrests cells completely in S phase.
C. Berthet, K. Raj, P. Saudan, and P. Beard (2005)
PNAS 102, 13634-13639
   Abstract »    Full Text »    PDF »
Role of Checkpoint Kinase 1 in Preventing Premature Mitosis in Response to Gemcitabine.
M. A. Morgan, L. A. Parsels, J. D. Parsels, A. K. Mesiwala, J. Maybaum, and T. S. Lawrence (2005)
Cancer Res. 65, 6835-6842
   Abstract »    Full Text »    PDF »
Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine.
R. A. Mesa, D. Loegering, H. L. Powell, K. Flatten, S. J. H. Arlander, N. T. Dai, M. P. Heldebrant, B. T. Vroman, B. D. Smith, J. E. Karp, et al. (2005)
Blood 106, 318-327
   Abstract »    Full Text »    PDF »
DNA Polymerase {kappa} Is Specifically Required for Recovery from the Benzo[a]pyrene-Dihydrodiol Epoxide (BPDE)-induced S-phase Checkpoint.
X. Bi, D. M. Slater, H. Ohmori, and C. Vaziri (2005)
J. Biol. Chem. 280, 22343-22355
   Abstract »    Full Text »    PDF »
Cytokine-driven cell cycling is mediated through Cdc25A.
A. R. Khaled, D. V. Bulavin, C. Kittipatarin, W. Q. Li, M. Alvarez, K. Kim, H. A. Young, A. J. Fornace, and S. K. Durum (2005)
J. Cell Biol. 169, 755-763
   Abstract »    Full Text »    PDF »
{beta}-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases.
Y. Kanemori, K. Uto, and N. Sagata (2005)
PNAS 102, 6279-6284
   Abstract »    Full Text »    PDF »
Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA Breakage.
R. G. Syljuasen, C. S. Sorensen, L. T. Hansen, K. Fugger, C. Lundin, F. Johansson, T. Helleday, M. Sehested, J. Lukas, and J. Bartek (2005)
Mol. Cell. Biol. 25, 3553-3562
   Abstract »    Full Text »    PDF »
The Role of Checkpoint Kinase 1 in Sensitivity to Topoisomerase I Poisons.
K. Flatten, N. T. Dai, B. T. Vroman, D. Loegering, C. Erlichman, L. M. Karnitz, and S. H. Kaufmann (2005)
J. Biol. Chem. 280, 14349-14355
   Abstract »    Full Text »    PDF »
Normal Cell Cycle and Checkpoint Responses in Mice and Cells Lacking Cdc25B and Cdc25C Protein Phosphatases.
A. M. Ferguson, L. S. White, P. J. Donovan, and H. Piwnica-Worms (2005)
Mol. Cell. Biol. 25, 2853-2860
   Abstract »    Full Text »    PDF »
Novel hydroxyl naphthoquinones with potent Cdc25 antagonizing and growth inhibitory properties.
V. P. Peyregne, S. Kar, S. W. Ham, M. Wang, Z. Wang, and B. I. Carr (2005)
Mol. Cancer Ther. 4, 595-602
   Abstract »    Full Text »    PDF »
p53 C-Terminal Phosphorylation by CHK1 and CHK2 Participates in the Regulation of DNA-Damage-induced C-Terminal Acetylation.
Y.-H. Ou, P.-H. Chung, T.-P. Sun, and S.-Y. Shieh (2005)
Mol. Biol. Cell 16, 1684-1695
   Abstract »    Full Text »    PDF »
TTK/hMps1 Participates in the Regulation of DNA Damage Checkpoint Response by Phosphorylating CHK2 on Threonine 68.
J.-H. Wei, Y.-F. Chou, Y.-H. Ou, Y.-H. Yeh, S.-W. Tyan, T.-P. Sun, C.-Y. Shen, and S.-Y. Shieh (2005)
J. Biol. Chem. 280, 7748-7757
   Abstract »    Full Text »    PDF »
Methylator-induced, Mismatch Repair-dependent G2 Arrest Is Activated through Chk1 and Chk2.
A. W. Adamson, D. I. Beardsley, W.-J. Kim, Y. Gao, R. Baskaran, and K. D. Brown (2005)
Mol. Biol. Cell 16, 1513-1526
   Abstract »    Full Text »    PDF »
The Cytokinin Requirement for Cell Division in Cultured Nicotiana plumbaginifolia Cells Can Be Satisfied by Yeast Cdc25 Protein Tyrosine Phosphatase. Implications for Mechanisms of Cytokinin Response and Plant Development.
K. Zhang, L. Diederich, and P. C.L. John (2005)
Plant Physiology 137, 308-316
   Abstract »    Full Text »    PDF »
On the Slowing of S Phase in Response to DNA Damage in Fission Yeast.
S. Kumar and J. A. Huberman (2004)
J. Biol. Chem. 279, 43574-43580
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882