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.

Science 4 December 1998:
Vol. 282. no. 5395, pp. 1893 - 1897
DOI: 10.1126/science.282.5395.1893
Prev | Table of Contents | Next

Reports

Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase

Shuhei Matsuoka, Mingxia Huang, Stephen J. Elledge *

In response to DNA damage and replication blocks, cells prevent cell cycle progression through the control of critical cell cycle regulators. We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints. Chk2 was rapidly phosphorylated and activated in response to replication blocks and DNA damage; the response to DNA damage occurred in an ataxia telangiectasia mutated (ATM)-dependent manner. In vitro, Chk2 phosphorylated Cdc25C on serine-216, a site known to be involved in negative regulation of Cdc25C. This is the same site phosphorylated by the protein kinase Chk1, which suggests that, in response to DNA damage and DNA replicational stress, Chk1 and Chk2 may phosphorylate Cdc25C to prevent entry into mitosis.

Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
*   To whom correspondence should be addressed. E-mail: selledge{at}bcm.tmc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor PV1019 [7-Nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide].
A. G. Jobson, G. T. Lountos, P. L. Lorenzi, J. Llamas, J. Connelly, D. Cerna, J. E. Tropea, A. Onda, G. Zoppoli, S. Kondapaka, et al. (2009)
J. Pharmacol. Exp. Ther. 331, 816-826
   Abstract »    Full Text »    PDF »
A Cds1-Mediated Checkpoint Protects the MBF Activator Rep2 from Ubiquitination by Anaphase-Promoting Complex/Cyclosome-Ste9 at S-Phase Arrest in Fission Yeast.
Z. Chu, M. Eshaghi, S. Y. Poon, and J. Liu (2009)
Mol. Cell. Biol. 29, 4959-4970
   Abstract »    Full Text »    PDF »
The combined status of ATM and p53 link tumor development with therapeutic response.
H. Jiang, H. C. Reinhardt, J. Bartkova, J. Tommiska, C. Blomqvist, H. Nevanlinna, J. Bartek, M. B. Yaffe, and M. T. Hemann (2009)
Genes & Dev. 23, 1895-1909
   Abstract »    Full Text »    PDF »
RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation.
S. Badie, C. Liao, M. Thanasoula, P. Barber, M. A. Hill, and M. Tarsounas (2009)
J. Cell Biol. 185, 587-600
   Abstract »    Full Text »    PDF »
Cisplatin Resistance of the HNSCC Cell Line UT-SCC-26A Can be Overcome by Stimulation of the EGF-Receptor.
R. MANDIC, C. J. RODGARKIA-DARA, V. KROHN, S. WIEGAND, R. GRENMAN, and J. A. WERNER (2009)
Anticancer Res 29, 1181-1187
   Abstract »    Full Text »    PDF »
Interference of cell cycle progression by zidovudine and lamivudine in NIH 3T3 cells.
J.-L. Fang, L. J. McGarrity, and F. A. Beland (2009)
Mutagenesis 24, 133-141
   Abstract »    Full Text »    PDF »
Levonorgestrel Enhances Spermatogenesis Suppression by Testosterone with Greater Alteration in Testicular Gene Expression in Men.
Y. Lue, C. Wang, Y. Cui, X. Wang, J. Sha, Z. Zhou, J. Xu, C. Wang, A. P. Sinha Hikim, and R. S. Swerdloff (2009)
Biol Reprod 80, 484-492
   Abstract »    Full Text »    PDF »
Chk2 Oligomerization Studied by Phosphopeptide Ligation: IMPLICATIONS FOR REGULATION AND PHOSPHODEPENDENT INTERACTIONS.
J. Li, I. A. Taylor, J. Lloyd, J. A. Clapperton, S. Howell, D. MacMillan, and S. J. Smerdon (2008)
J. Biol. Chem. 283, 36019-36030
   Abstract »    Full Text »    PDF »
Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo.
J. A. Daniel, M. Pellegrini, J.-H. Lee, T. T. Paull, L. Feigenbaum, and A. Nussenzweig (2008)
J. Cell Biol. 183, 777-783
   Abstract »    Full Text »    PDF »
Enterococcus faecalis Induces Aneuploidy and Tetraploidy in Colonic Epithelial Cells through a Bystander Effect.
X. Wang, T. D. Allen, R. J. May, S. Lightfoot, C. W. Houchen, and M. M. Huycke (2008)
Cancer Res. 68, 9909-9917
   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 »
Regulation of Chk2 Ubiquitination and Signaling through Autophosphorylation of Serine 379.
C. M. Lovly, L. Yan, C. E. Ryan, S. Takada, and H. Piwnica-Worms (2008)
Mol. Cell. Biol. 28, 5874-5885
   Abstract »    Full Text »    PDF »
The DNA Damage Sensors Ataxia-Telangiectasia Mutated Kinase and Checkpoint Kinase 2 Are Required for Hepatitis C Virus RNA Replication.
Y. Ariumi, M. Kuroki, H. Dansako, K.-I. Abe, M. Ikeda, T. Wakita, and N. Kato (2008)
J. Virol. 82, 9639-9646
   Abstract »    Full Text »    PDF »
Cellular commitment to reentry into the cell cycle after stalled DNA is determined by site-specific phosphorylation of Chk1 and PTEN.
S. A. Martin and T. Ouchi (2008)
Mol. Cancer Ther. 7, 2509-2516
   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 »
Regulation of TIP60 by ATF2 Modulates ATM Activation.
A. Bhoumik, N. Singha, M. J. O'Connell, and Z. A. Ronai (2008)
J. Biol. Chem. 283, 17605-17614
   Abstract »    Full Text »    PDF »
RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205.
J. Yan, X.-P. Yang, Y.-S. Kim, and A. M. Jetten (2008)
Cancer Res. 68, 4269-4276
   Abstract »    Full Text »    PDF »
Activated neutrophils induce an hMSH2-dependent G2/M checkpoint arrest and replication errors at a (CA)13-repeat in colon epithelial cells.
C Campregher, M G Luciani, and C Gasche (2008)
Gut 57, 780-787
   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 »
RNF8-dependent and RNF8-independent Regulation of 53BP1 in Response to DNA Damage.
R. Sakasai and R. Tibbetts (2008)
J. Biol. Chem. 283, 13549-13555
   Abstract »    Full Text »    PDF »
Ku is involved in cell growth, DNA replication and G1-S transition.
E. Rampakakis, D. Di Paola, and M. Zannis-Hadjopoulos (2008)
J. Cell Sci. 121, 590-600
   Abstract »    Full Text »    PDF »
TLR9 engagement on CD4 T lymphocytes represses {gamma}-radiation-induced apoptosis through activation of checkpoint kinase response elements.
L. Zheng, N. Asprodites, A. H. Keene, P. Rodriguez, K. D. Brown, and E. Davila (2008)
Blood 111, 2704-2713
   Abstract »    Full Text »    PDF »
ATR signaling can drive cells into senescence in the absence of DNA breaks.
L. I. Toledo, M. Murga, P. Gutierrez-Martinez, R. Soria, and O. Fernandez-Capetillo (2008)
Genes & Dev. 22, 297-302
   Abstract »    Full Text »    PDF »
ATR Pathway Is the Primary Pathway for Activating G2/M Checkpoint Induction After Re-replication.
J. J. Lin and A. Dutta (2007)
J. Biol. Chem. 282, 30357-30362
   Abstract »    Full Text »    PDF »
Stability of Checkpoint Kinase 2 Is Regulated via Phosphorylation at Serine 456.
E. M. Kass, J. Ahn, T. Tanaka, W. A. Freed-Pastor, S. Keezer, and C. Prives (2007)
J. Biol. Chem. 282, 30311-30321
   Abstract »    Full Text »    PDF »
Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts.
A. Errico, V. Costanzo, and T. Hunt (2007)
PNAS 104, 14929-14934
   Abstract »    Full Text »    PDF »
Identification and Biological Evaluation of a Novel and Potent Small Molecule Radiation Sensitizer via an Unbiased Screen of a Chemical Library.
B. E. Lally, G. A. Geiger, S. Kridel, A. E. Arcury-Quandt, M. E. Robbins, N. D. Kock, K. Wheeler, P. Peddi, A. Georgakilas, G. D. Kao, et al. (2007)
Cancer Res. 67, 8791-8799
   Abstract »    Full Text »    PDF »
The Role of the DNA Damage Checkpoint Pathway in Intraductal Papillary Mucinous Neoplasms of the Pancreas.
Y. Miyasaka, E. Nagai, H. Yamaguchi, K. Fujii, T. Inoue, K. Ohuchida, T. Yamada, K. Mizumoto, M. Tanaka, and M. Tsuneyoshi (2007)
Clin. Cancer Res. 13, 4371-4377
   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 »
Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line.
A. Herman-Antosiewicz, H. Xiao, K. L. Lew, and S. V. Singh (2007)
Mol. Cancer Ther. 6, 1673-1681
   Abstract »    Full Text »    PDF »
Modulation of Cell Cycle-specific Gene Expressions at the Onset of S Phase Arrest Contributes to the Robust DNA Replication Checkpoint Response in Fission Yeas.
Z. Chu, J. Li, M. Eshaghi, X. Peng, R. K. M. Karuturi, and J. Liu (2007)
Mol. Biol. Cell 18, 1756-1767
   Abstract »    Full Text »    PDF »
S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells.
S. Ray, S. Shyam, G. C. Fraizer, and A. Almasan (2007)
Mol. Cancer Ther. 6, 1368-1378
   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 »
Cross-talk between Chk1 and Chk2 in double-mutant thymocytes.
K. Zaugg, Y.-W. Su, P. T. Reilly, Y. Moolani, C. C. Cheung, R. Hakem, A. Hirao, Q. Liu, S. J. Elledge, and T. W. Mak (2007)
PNAS 104, 3805-3810
   Abstract »    Full Text »    PDF »
Biochemical and cellular characterization of VRX0466617, a novel and selective inhibitor for the checkpoint kinase Chk2.
L. Carlessi, G. Buscemi, G. Larson, Z. Hong, J. Z. Wu, and D. Delia (2007)
Mol. Cancer Ther. 6, 935-944
   Abstract »    Full Text »    PDF »
The Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 directly influence the DNA damage-dependent functions of Rad53.
T. Usui and J. H. J. Petrini (2007)
PNAS 104, 2797-2802
   Abstract »    Full Text »    PDF »
Circadian Output, Input, and Intracellular Oscillators: Insights into the Circadian Systems of Single Cells.
J. J. Loros, J. C. Dunlap, L. F. Larrondo, M. Shi, W. J. Belden, V. D. Gooch, C.-H. Chen, C. L. Baker, A. Mehra, H. V. Colot, et al. (2007)
Cold Spring Harb Symp Quant Biol 72, 201-214
   Abstract »    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 »
EDD Mediates DNA Damage-induced Activation of CHK2.
M. J. Henderson, M. A. Munoz, D. N. Saunders, J. L. Clancy, A. J. Russell, B. Williams, D. Pappin, K. K. Khanna, S. P. Jackson, R. L. Sutherland, et al. (2006)
J. Biol. Chem. 281, 39990-40000
   Abstract »    Full Text »    PDF »
Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells.
C. Agarwal, A. Tyagi, and R. Agarwal (2006)
Mol. Cancer Ther. 5, 3294-3302
   Abstract »    Full Text »    PDF »
DNA Damage-Induced Cell Cycle Regulation and Function of Novel Chk2 Phosphoresidues.
G. Buscemi, L. Carlessi, L. Zannini, S. Lisanti, E. Fontanella, S. Canevari, and D. Delia (2006)
Mol. Cell. Biol. 26, 7832-7845
   Abstract »    Full Text »    PDF »
DDB1 Maintains Genome Integrity through Regulation of Cdt1.
C. A. Lovejoy, K. Lock, A. Yenamandra, and D. Cortez (2006)
Mol. Cell. Biol. 26, 7977-7990
   Abstract »    Full Text »    PDF »
CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage.
E. Schmitt, R. Boutros, C. Froment, B. Monsarrat, B. Ducommun, and C. Dozier (2006)
J. Cell Sci. 119, 4269-4275
   Abstract »    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 Involvement of Ataxia-telangiectasia Mutated Protein Activation in Nucleotide Excision Repair-facilitated Cell Survival with Cisplatin Treatment.
S. L. Colton, X. S. Xu, Y. A. Wang, and G. Wang (2006)
J. Biol. Chem. 281, 27117-27125
   Abstract »    Full Text »    PDF »
Differential Roles of ATM- and Chk2-Mediated Phosphorylations of Hdmx in Response to DNA Damage..
Y. Pereg, S. Lam, A. Teunisse, S. Biton, E. Meulmeester, L. Mittelman, G. Buscemi, K. Okamoto, Y. Taya, Y. Shiloh, et al. (2006)
Mol. Cell. Biol. 26, 6819-6831
   Abstract »    Full Text »    PDF »
Intrinsic Kinase Activity and SQ/TQ Domain of Chk2 Kinase as Well as N-terminal Domain of Wip1 Phosphatase Are Required for Regulation of Chk2 by Wip1.
A. Yoda, X. Z. Xu, N. Onishi, K. Toyoshima, H. Fujimoto, N. Kato, I. Oishi, T. Kondo, and Y. Minami (2006)
J. Biol. Chem. 281, 24847-24862
   Abstract »    Full Text »    PDF »
The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles.
A. M. Pregueiro, Q. Liu, C. L. Baker, J. C. Dunlap, and J. J. Loros (2006)
Science 313, 644-649
   Abstract »    Full Text »    PDF »
Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia.
M. F. Rudd, G. S. Sellick, E. L. Webb, D. Catovsky, and R. S. Houlston (2006)
Blood 108, 638-644
   Abstract »    Full Text »    PDF »
Deregulation of DNA Damage Signal Transduction by Herpesvirus Latency-Associated M2..
X. Liang, M. T. Pickering, N.-H. Cho, H. Chang, M. R. Volkert, T. F. Kowalik, and J. U. Jung (2006)
J. Virol. 80, 5862-5874
   Abstract »    Full Text »    PDF »
Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals.
P. E. Cohen, S. E. Pollack, and J. W. Pollard (2006)
Endocr. Rev. 27, 398-426
   Abstract »    Full Text »    PDF »
Amino Acids C-Terminal to the 14-3-3 Binding Motif in CDC25B Affect the Efficiency of 14-3-3 Binding..
S. Uchida, A. Kubo, R. Kizu, H. Nakagama, T. Matsunaga, Y. Ishizaka, and K. Yamashita (2006)
J. Biochem. 139, 761-769
   Abstract »    Full Text »    PDF »
Effect of combined DNA repair inhibition and G2 checkpoint inhibition on cell cycle progression after DNA damage..
C. M. Sturgeon, Z. A. Knight, K. M. Shokat, and M. Roberge (2006)
Mol. Cancer Ther. 5, 885-892
   Abstract »    Full Text »    PDF »
Proliferating Human Cells Hypomorphic for Origin Recognition Complex 2 and Pre-replicative Complex Formation Have a Defect in p53 Activation and Cdk2 Kinase Activation.
J. K. Teer, Y. J. Machida, H. Labit, O. Novac, O. Hyrien, K. Marheineke, M. Zannis-Hadjopoulos, and A. Dutta (2006)
J. Biol. Chem. 281, 6253-6260
   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 »
Stalled Replication Induces p53 Accumulation through Distinct Mechanisms from DNA Damage Checkpoint Pathways.
C. C. Ho, W. Y. Siu, A. Lau, W. M. Chan, T. Arooz, and R. Y.C. Poon (2006)
Cancer Res. 66, 2233-2241
   Abstract »    Full Text »    PDF »
Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication in human cells.
T. Hiyama, M. Katsura, T. Yoshihara, M. Ishida, A. Kinomura, T. Tonda, T. Asahara, and K. Miyagawa (2006)
Nucleic Acids Res. 34, 880-892
   Abstract »    Full Text »    PDF »
DNA damage checkpoints in mammals.
H. Niida and M. Nakanishi (2006)
Mutagenesis 21, 3-9
   Abstract »    Full Text »    PDF »
The Role of Polo-like Kinase 1 in the Inhibition of Centrosome Separation after Ionizing Radiation.
W. Zhang, L. Fletcher, and R. J. Muschel (2005)
J. Biol. Chem. 280, 42994-42999
   Abstract »    Full Text »    PDF »
Changes in Regulatory Phosphorylation of Cdc25C Ser287 and Wee1 Ser549 during Normal Cell Cycle Progression and Checkpoint Arrests.
J. S. Stanford and J. V. Ruderman (2005)
Mol. Biol. Cell 16, 5749-5760
   Abstract »    Full Text »    PDF »
DNA Damage Regulates Chk2 Association with Chromatin.
J. Li and D. F. Stern (2005)
J. Biol. Chem. 280, 37948-37956
   Abstract »    Full Text »    PDF »
Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3 cells.
A. Tyagi, R. P. Singh, C. Agarwal, S. Siriwardana, R. A. Sclafani, and R. Agarwal (2005)
Carcinogenesis 26, 1978-1987
   Abstract »    Full Text »    PDF »
p53-Independent Regulation of p21Waf1/Cip1 Expression and Senescence by Chk2.
C.-M. Aliouat-Denis, N. Dendouga, I. Van den Wyngaert, H. Goehlmann, U. Steller, I. van de Weyer, N. Van Slycken, L. Andries, S. Kass, W. Luyten, et al. (2005)
Mol. Cancer Res. 3, 627-634
   Abstract »    Full Text »    PDF »
Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation.
J. Turner, C. Koumenis, T. E. Kute, R. P. Planalp, M. W. Brechbiel, D. Beardsley, B. Cody, K. D. Brown, F. M. Torti, and S. V. Torti (2005)
Blood 106, 3191-3199
   Abstract »    Full Text »    PDF »
BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly.
S.-Y. Lin, R. Rai, K. Li, Z.-X. Xu, and S. J. Elledge (2005)
PNAS 102, 15105-15109
   Abstract »    Full Text »    PDF »
Impaired hepatocyte survival and liver regeneration in Atm-deficient mice.
S. Lu, K. C. Shen, Y. Wang, S.C. Brooks, and Y. A. Wang (2005)
Hum. Mol. Genet. 14, 3019-3025
   Abstract »    Full Text »    PDF »
N-Methyl-N'-nitro-N-nitrosoguanidine Activates Cell-Cycle Arrest through Distinct Mechanisms Activated in a Dose-Dependent Manner.
D. I. Beardsley, W.-J. Kim, and K. D. Brown (2005)
Mol. Pharmacol. 68, 1049-1060
   Abstract »    Full Text »    PDF »
Checkpoint Kinase 1 Regulates Diallyl Trisulfide-induced Mitotic Arrest in Human Prostate Cancer Cells.
A. Herman-Antosiewicz and S. V. Singh (2005)
J. Biol. Chem. 280, 28519-28528
   Abstract »    Full Text »    PDF »
NBS1 Knockdown by Small Interfering RNA Increases Ionizing Radiation Mutagenesis and Telomere Association in Human Cells.
Y. Zhang, C. U.K. Lim, E. S. Williams, J. Zhou, Q. Zhang, M. H. Fox, S. M. Bailey, and H. L. Liber (2005)
Cancer Res. 65, 5544-5553
   Abstract »    Full Text »    PDF »
Akt Activation Suppresses Chk2-Mediated, Methylating Agent-Induced G2 Arrest and Protects from Temozolomide-Induced Mitotic Catastrophe and Cellular Senescence.
Y. Hirose, M. Katayama, O. K. Mirzoeva, M. S. Berger, and R. O. Pieper (2005)
Cancer Res. 65, 4861-4869
   Abstract »    Full Text »    PDF »
Grp/DChk1 is required for G2-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable.
H. I. de Vries, L. Uyetake, W. Lemstra, J. F. Brunsting, T. T. Su, H. H. Kampinga, and O. C. M. Sibon (2005)
J. Cell Sci. 118, 1833-1842
   Abstract »    Full Text »    PDF »
RNA Silencing of Checkpoint Regulators Sensitizes p53-Defective Prostate Cancer Cells to Chemotherapy while Sparing Normal Cells.
U. K. Mukhopadhyay, A. M. Senderowicz, and G. Ferbeyre (2005)
Cancer Res. 65, 2872-2881
   Abstract »    Full Text »    PDF »
Regulation of CHK2 by DNA-dependent Protein Kinase.
J. Li and D. F. Stern (2005)
J. Biol. Chem. 280, 12041-12050
   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 »
Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.
A. Shaag, T. Walsh, P. Renbaum, T. Kirchhoff, K. Nafa, S. Shiovitz, J. B. Mandell, P. Welcsh, M. K. Lee, N. Ellis, et al. (2005)
Hum. Mol. Genet. 14, 555-563
   Abstract »    Full Text »    PDF »
Interchromosomal segmental duplications of the pericentromeric region on the human Y chromosome.
S. Kirsch, B. Weiss, T. L. Miner, R. H. Waterston, R. A. Clark, E. E. Eichler, C. Munch, W. Schempp, and G. Rappold (2005)
Genome Res. 15, 195-204
   Abstract »    Full Text »    PDF »
Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells.
L.-H. Yih, S.-W. Hsueh, W.-S. Luu, T. H. Chiu, and T.-C. Lee (2005)
Carcinogenesis 26, 53-63
   Abstract »    Full Text »    PDF »
p73 induction after DNA damage is regulated by checkpoint kinases Chk1 and Chk2.
M. Urist, T. Tanaka, M. V. Poyurovsky, and C. Prives (2004)
Genes & Dev. 18, 3041-3054
   Abstract »    Full Text »    PDF »
A Role for the Fanconi Anemia C Protein in Maintaining the DNA Damage-induced G2 Checkpoint.
B. W. Freie, S. L. M. Ciccone, X. Li, P. A. Plett, C. M. Orschell, E. F. Srour, H. Hanenberg, D. Schindler, S.-H. Lee, and D. W. Clapp (2004)
J. Biol. Chem. 279, 50986-50993
   Abstract »    Full Text »    PDF »
Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends.
T. D. McSherry and P. R. Mueller (2004)
Mol. Cell. Biol. 24, 9968-9985
   Abstract »    Full Text »    PDF »
The Stress Kinase MRK Contributes to Regulation of DNA Damage Checkpoints through a p38{gamma}-independent Pathway.
E. Tosti, L. Waldbaum, G. Warshaw, E. A. Gross, and R. Ruggieri (2004)
J. Biol. Chem. 279, 47652-47660
   Abstract »    Full Text »    PDF »
Statins Enhance Migratory Capacity by Upregulation of the Telomere Repeat-Binding Factor TRF2 in Endothelial Progenitor Cells.
I. Spyridopoulos, J. Haendeler, C. Urbich, T. H. Brummendorf, H. Oh, M. D. Schneider, A. M. Zeiher, and S. Dimmeler (2004)
Circulation 110, 3136-3142
   Abstract »    Full Text »    PDF »
Locked Nucleic Acid-Enhanced Detection of 1100delC*CHEK2 Germ-Line Mutation in Spanish Patients with Hematologic Malignancies.
M. Collado, O. Landt, E. Barragan, U. Lass, J. Cervera, M. A. Sanz, and P. Bolufer (2004)
Clin. Chem. 50, 2201-2204
   Full Text »    PDF »
Germline CHEK2*1100delC mutations in breast cancer patients with multiple primary cancers.
J Huang, S M Domchek, M S Brose, T R Rebbeck, K L Nathanson, and B L Weber (2004)
J. Med. Genet. 41, e120
   Full Text »    PDF »
ATM-dependent CHK2 Activation Induced by Anticancer Agent, Irofulven.
J. Wang, T. Wiltshire, Y. Wang, C. Mikell, J. Burks, C. Cunningham, E. S. Van Laar, S. J. Waters, E. Reed, and W. Wang (2004)
J. Biol. Chem. 279, 39584-39592
   Abstract »    Full Text »    PDF »
Potentiation of Cytotoxicity of Topoisomerase I Poison by Concurrent and Sequential Treatment with the Checkpoint Inhibitor UCN-01 Involves Disparate Mechanisms Resulting in Either p53-Independent Clonogenic Suppression or p53-Dependent Mitotic Catastrophe.
A. N. Tse and G. K. Schwartz (2004)
Cancer Res. 64, 6635-6644
   Abstract »    Full Text »    PDF »
Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality.
K. M. Hopkins, W. Auerbach, X. Y. Wang, M. P. Hande, H. Hang, D. J. Wolgemuth, A. L. Joyner, and H. B. Lieberman (2004)
Mol. Cell. Biol. 24, 7235-7248
   Abstract »    Full Text »    PDF »
BRCA1-BARD1 Complexes Are Required for p53Ser-15 Phosphorylation and a G1/S Arrest following Ionizing Radiation-induced DNA Damage.
M. Fabbro, K. Savage, K. Hobson, A. J. Deans, S. N. Powell, G. A. McArthur, and K. K. Khanna (2004)
J. Biol. Chem. 279, 31251-31258
   Abstract »    Full Text »    PDF »
Differentiation-Induced Radioresistance in Muscle Cells.
L. Latella, J. Lukas, C. Simone, P. L. Puri, and J. Bartek (2004)
Mol. Cell. Biol. 24, 6350-6361
   Abstract »    Full Text »    PDF »
Binding of 14-3-3{beta} but not 14-3-3{sigma} controls the cytoplasmic localization of CDC25B: binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B.
S. Uchida, A. Kuma, M. Ohtsubo, M. Shimura, M. Hirata, H. Nakagama, T. Matsunaga, Y. Ishizaka, and K. Yamashita (2004)
J. Cell Sci. 117, 3011-3020
   Abstract »    Full Text »    PDF »
Negative Regulation of Chk2 Expression by p53 Is Dependent on the CCAAT-binding Transcription Factor NF-Y.
T. Matsui, Y. Katsuno, T. Inoue, F. Fujita, T. Joh, H. Niida, H. Murakami, M. Itoh, and M. Nakanishi (2004)
J. Biol. Chem. 279, 25093-25100
   Abstract »    Full Text »    PDF »
Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C.
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 (2004)
J. Biol. Chem. 279, 25813-25822
   Abstract »    Full Text »    PDF »
The Molecular Pathology of Primary Immunodeficiencies.
M. S. Lim and K. S.J. Elenitoba-Johnson (2004)
J. Mol. Diagn. 6, 59-83
   Full Text »    PDF »
DNA damage responses triggered by a highly cytotoxic monofunctional DNA alkylator, hedamycin, a pluramycin antitumor antibiotic.
L. C. Tu, T. Melendy, and T. A. Beerman (2004)
Mol. Cancer Ther. 3, 577-586
   Abstract »    Full Text »    PDF »
Rad9 Protects Cells from Topoisomerase Poison-induced Cell Death.
D. Loegering, S. J. H. Arlander, J. Hackbarth, B. T. Vroman, P. Roos-Mattjus, K. M. Hopkins, H. B. Lieberman, L. M. Karnitz, and S. H. Kaufmann (2004)
J. Biol. Chem. 279, 18641-18647
   Abstract »    Full Text »    PDF »
Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation.
S.-Y. Lin, K. Li, G. S. Stewart, and S. J. Elledge (2004)
PNAS 101, 6484-6489
   Abstract »    Full Text »    PDF »
A Cleaved Form of MAGE-A4 Binds to Miz-1 and Induces Apoptosis in Human Cells.
T. Sakurai, K. Itoh, H. Higashitsuji, T. Nagao, K. Nonoguchi, T. Chiba, and J. Fujita (2004)
J. Biol. Chem. 279, 15505-15514
   Abstract »    Full Text »    PDF »
Apoptosis Associated with Deregulated E2F Activity Is Dependent on E2F1 and Atm/Nbs1/Chk2.
H. A. Rogoff, M. T. Pickering, F. M. Frame, M. E. Debatis, Y. Sanchez, S. Jones, and T. F. Kowalik (2004)
Mol. Cell. Biol. 24, 2968-2977
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)