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Science 287 (5459): 1765-1766

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

Piecing Together the p53 Puzzle

Antony M. Carr

When the DNA of a cell is damaged, a network of proteins tell the cell to stop at the nearest cell cycle checkpoint so that the DNA repair machinery can set about shoring up the damage and the cell can decide whether to continue proliferating. In a Perspective, Carr discusses new findings (Hirao et al.) showing that the checkpoint kinase CHK2 regulates a crucial central player in checkpoint pathways-the tumor suppressor protein p53.

The author is at the MRC Cell Mutation Unit, Sussex University, Falmer, Brighton BN1 9RR, UK. E-mail: a.m.carr{at}

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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)
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Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes.
F. M. Bastos de Oliveira, M. R. Harris, P. Brazauskas, R. A. M. de Bruin, and M. B. Smolka (2012)
EMBO J. 31, 1798-1810
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K. Argiris, C. Panethymitaki, and M. Tavassoli (2011)
Experimental Biology and Medicine 236, 524-536
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Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose {gamma}-irradiation.
H. Yu, H. Shen, Y. Yuan, R. XuFeng, X. Hu, S. P. Garrison, L. Zhang, J. Yu, G. P. Zambetti, and T. Cheng (2010)
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Restoration of p53 Functions Protects Cells from Concanavalin A-Induced Apoptosis.
A.R.M. R. Amin, V. S. Thakur, K. Gupta, M. W. Jackson, H. Harada, M. K. Agarwal, D. M. Shin, D. N. Wald, and M. L. Agarwal (2010)
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   Abstract »    Full Text »    PDF »
Perspectives for Cancer Prevention With Natural Compounds.
A.R.M. R. Amin, O. Kucuk, F. R. Khuri, and D. M. Shin (2009)
J. Clin. Oncol. 27, 2712-2725
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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)
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Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by cooperating in trans-activation of bax expression.
V. S. Budhram-Mahadeo, S. Bowen, S. Lee, C. Perez-Sanchez, E. Ensor, P. J. Morris, and D. S. Latchman (2006)
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Base Excision Repair Intermediates Induce p53-independent Cytotoxic and Genotoxic Responses.
R. W. Sobol, M. Kartalou, K. H. Almeida, D. F. Joyce, B. P. Engelward, J. K. Horton, R. Prasad, L. D. Samson, and S. H. Wilson (2003)
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S. Harris, C. Kemplen, T. Caspari, C. Chan, H. D. Lindsay, M. Poitelea, A. M. Carr, and C. Price (2003)
J. Cell Sci. 116, 3519-3529
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A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein.
N. Foray, D. Marot, A. Gabriel, V. Randrianarison, A. M. Carr, M. Perricaudet, A. Ashworth, and P. Jeggo (2003)
EMBO J. 22, 2860-2871
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p53 Transgenic Mice Are Highly Susceptible to 1, 2-Dimethylhydrazine-induced Uterine Sarcomas.
Z. Zhang, J. Li, L. E. Lantry, Y. Wang, R. W. Wiseman, R. A. Lubet, and M. You (2002)
Cancer Res. 62, 3024-3029
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Functions of BRCA1 and BRCA2 in the biological response to DNA damage.
A. R. Venkitaraman (2001)
J. Cell Sci. 114, 3591-3598
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Mechanism of Apoptosis and Determination of Cellular Fate in Chromium(VI)-exposed Populations of Telomerase-immortalized Human Fibroblasts.
D. E. Pritchard, S. Ceryak, L. Ha, J. L. Fornsaglio, S. K. Hartman, T. J. O'Brien, and S. R. Patierno (2001)
Cell Growth Differ. 12, 487-496
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COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system.
D. Bech-Otschir, R. Kraft, X. Huang, P. Henklein, B. Kapelari, C. Pollmann, and W. Dubiel (2001)
EMBO J. 20, 1630-1639
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Phosphorylation and Rapid Relocalization of 53BP1 to Nuclear Foci upon DNA Damage.
L. Anderson, C. Henderson, and Y. Adachi (2001)
Mol. Cell. Biol. 21, 1719-1729
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Chromosome 11 allelotypes reflect a mechanism of chemical carcinogenesis in heterozygous p53-deficient mice.
J. E. Hulla, J. E. French, and J. K. Dunnick (2001)
Carcinogenesis 22, 89-98
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Loss of heterozygosity frequency at the Trp53 locus in p53-deficient (+/-) mouse tumors is carcinogen-and tissue-dependent.
J. E. French, G. D. Lacks, C. Trempus, J. K. Dunnick, J. Foley, J. Mahler, R. R. Tice, and R. W. Tennant (2001)
Carcinogenesis 22, 99-106
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Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.
C. L. Limoli, E. Giedzinski, W. F. Morgan, and J. E. Cleaver (2000)
PNAS 97, 7939-7946
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Transcriptional Regulation of the Human DNA Polymerase delta Catalytic Subunit Gene POLD1 by p53 Tumor Suppressor and Sp1.
B. Li and M. Y. W. Lee (2001)
J. Biol. Chem. 276, 29729-29739
   Abstract »    Full Text »    PDF »
Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.
C. L. Limoli, E. Giedzinski, W. F. Morgan, and J. E. Cleaver (2000)
PNAS 97, 7939-7946
   Abstract »    Full Text »    PDF »

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