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Science 20 November 1998:
Vol. 282. no. 5393, pp. 1497 - 1501
DOI: 10.1126/science.282.5393.1497
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Reports

Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage

F. Bunz, A. Dutriaux, C. Lengauer, T. Waldman, S. Zhou, J. P. Brown, J. M. Sedivy, K. W. Kinzler, B. Vogelstein *

After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma  radiated cells progressed into mitosis and exhibited a G2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells.

F. Bunz, S. Zhou, B. Vogelstein, The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA. C. Lengauer and K. W. Kinzler, The Johns Hopkins Oncology Center, Baltimore, MD 21231, USA. A. Dutriaux, J. P. Brown, J. Sedivy, Department of Molecular Biology, Cell Biology, and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA. T. Waldman, Program in Human Genetics and the Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
*   To whom correspondence should be addressed. E-mail: vogelbe{at}welchlink.welch.jhu.edu

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Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca2+ accumulation in colonocytes.
S. S. N. Kolar, R. Barhoumi, E. S. Callaway, Y.-Y. Fan, N. Wang, J. R. Lupton, and R. S. Chapkin (2007)
Am J Physiol Gastrointest Liver Physiol 293, G935-G943
   Abstract »    Full Text »    PDF »
The Alternative Reading Frame Tumor Suppressor Antagonizes Hypoxia-Induced Cancer Cell Migration via Interaction with the COOH-Terminal Binding Protein Corepressor.
S. Paliwal, R. C. Kovi, B. Nath, Y.-W. Chen, B. C. Lewis, and S. R. Grossman (2007)
Cancer Res. 67, 9322-9329
   Abstract »    Full Text »    PDF »
Methylation-Acetylation Interplay Activates p53 in Response to DNA Damage.
G. S. Ivanov, T. Ivanova, J. Kurash, A. Ivanov, S. Chuikov, F. Gizatullin, E. M. Herrera-Medina, F. Rauscher III, D. Reinberg, and N. A. Barlev (2007)
Mol. Cell. Biol. 27, 6756-6769
   Abstract »    Full Text »    PDF »
Aspirin blocks proliferation in colon cells by inducing a G1 arrest and apoptosis through activation of the checkpoint kinase ATM.
M.G. Luciani, C. Campregher, and C. Gasche (2007)
Carcinogenesis 28, 2207-2217
   Abstract »    Full Text »    PDF »
Identification of a Bis-guanylhydrazone [4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a Novel Chemotype for Inhibition of Chk2 Kinase.
A. G. Jobson, J. H. Cardellina II, D. Scudiero, S. Kondapaka, H. Zhang, H. Kim, R. Shoemaker, and Y. Pommier (2007)
Mol. Pharmacol. 72, 876-884
   Abstract »    Full Text »    PDF »
Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells.
H. Tazawa, N. Tsuchiya, M. Izumiya, and H. Nakagama (2007)
PNAS 104, 15472-15477
   Abstract »    Full Text »    PDF »
Cell Cycle Disturbances and Mitotic Catastrophes in HeLa Hep2 Cells following 2.5 to 10 Gy of Ionizing Radiation.
D. Eriksson, P.-O. Lofroth, L. Johansson, K. A. Riklund, and T. Stigbrand (2007)
Clin. Cancer Res. 13, 5501s-5508s
   Abstract »    Full Text »    PDF »
Activation of p53 by MEG3 Non-coding RNA.
Y. Zhou, Y. Zhong, Y. Wang, X. Zhang, D. L. Batista, R. Gejman, P. J. Ansell, J. Zhao, C. Weng, and A. Klibanski (2007)
J. Biol. Chem. 282, 24731-24742
   Abstract »    Full Text »    PDF »
The Early Response to DNA Damage Can Lead to Activation of Alternative Splicing Activity Resulting in CD44 Splice Pattern Changes.
V. Filippov, M. Filippova, and P. J. Duerksen-Hughes (2007)
Cancer Res. 67, 7621-7630
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Cells with Defective p53-p21-pRb Pathway Are Susceptible to Apoptosis Induced by p84N5 via Caspase-6.
E. Garner, F. Martinon, J. Tschopp, P. Beard, and K. Raj (2007)
Cancer Res. 67, 7631-7637
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A Functional Role for p38 MAPK in Modulating Mitotic Transit in the Absence of Stress.
H. Cha, X. Wang, H. Li, and A. J. Fornace Jr. (2007)
J. Biol. Chem. 282, 22984-22992
   Abstract »    Full Text »    PDF »
Evidence for Cooperative Transforming Activity of the Human Pituitary Tumor Transforming Gene and Human T-Cell Leukemia Virus Type 1 Tax.
S. V. Sheleg, J.-M. Peloponese, Y.-H. Chi, Y. Li, M. Eckhaus, and K.-T. Jeang (2007)
J. Virol. 81, 7894-7901
   Abstract »    Full Text »    PDF »
Splicing Regulator SC35 Is Essential for Genomic Stability and Cell Proliferation during Mammalian Organogenesis.
R. Xiao, Y. Sun, J.-H. Ding, S. Lin, D. W. Rose, M. G. Rosenfeld, X.-D. Fu, and X. Li (2007)
Mol. Cell. Biol. 27, 5393-5402
   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 »
Cancer Cells and Normal Cells Differ in Their Requirements for Thoc1.
Y. Li, A. W. Lin, X. Zhang, Y. Wang, X. Wang, and D. W. Goodrich (2007)
Cancer Res. 67, 6657-6664
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Induction of Cullin 7 by DNA damage attenuates p53 function.
P. Jung, B. Verdoodt, A. Bailey, J. R. Yates III, A. Menssen, and H. Hermeking (2007)
PNAS 104, 11388-11393
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Quantitative Assessment of the p53-Mdm2 Feedback Loop Using Protein Lysate Microarrays.
S. Ramalingam, P. Honkanen, L. Young, T. Shimura, J. Austin, P. S. Steeg, and S. Nishizuka (2007)
Cancer Res. 67, 6247-6252
   Abstract »    Full Text »    PDF »
p53-Dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion.
A.-H. Zhang, J. N. Rao, T. Zou, L. Liu, B. S. Marasa, L. Xiao, J. Chen, D. J. Turner, and J.-Y. Wang (2007)
Am J Physiol Cell Physiol 293, C379-C389
   Abstract »    Full Text »    PDF »


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