Carcinogenesis, Vol. 22, No. 6, 851-860,
June 2001
© 2001 Oxford University Press
COMMENTARY |
p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding
Department of Dermatology and Oregon Cancer Center, Oregon Health Sciences University, Portland, OR 97201, USA
Our environment contains physical, chemical and pathological agents that challenge the integrity of our DNA. In addition to DNA repair, higher multicellular organisms have evolved multiple pathways of response to damage including programmed cell death—apoptosis. The p53 protein appears to sense multiple types of DNA damage and coordinate with multiple options for cellular response. The p53 protein activities depend upon its DNA binding. Specific p53 protein post-translational modifications are required for efficient sequence-specific binding and transcriptional activities. Non-sequence-specific DNA binding may involve a wide spectrum of p53 proteins and predominate as DNA damage is more severe or p53 protein is more highly induced. p53 protein is not strictly required for DNA damage sensing and repair. Rather, p53 protein may govern an apoptosis checkpoint through competition with DNA repair proteins for non-sequence-specific binding to exposed single-stranded regions in the DNA duplex. This model provides a framework for testing mechanisms of p53-mediated apoptosis dependent upon the p53 protein modification state, the level of p53 protein accumulation, the level of DNA damage and the capacity of the damaged cell to repair.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Kress, A. Rezza, J. Nadjar, J. Samarut, and M. Plateroti The Thyroid Hormone Receptor-{alpha} (TR{alpha}) Gene Encoding TR{alpha}1 Controls Deoxyribonucleic Acid Damage-Induced Tissue Repair Mol. Endocrinol., January 1, 2008; 22(1): 47 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Casavant, M. H. Luo, K. Rosenke, T. Winegardner, A. Zurawska, and E. A. Fortunato Potential Role for p53 in the Permissive Life Cycle of Human Cytomegalovirus. J. Virol., September 1, 2006; 80(17): 8390 - 8401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H.C. Dirksen, J. Cloos, B. J.M. Braakhuis, R. H. Brakenhoff, A. J.R. Heck, and M. Slijper Human Lymphoblastoid Proteome Analysis Reveals a Role for the Inhibitor of Acetyltransferases Complex in DNA Double-Strand Break Response Cancer Res., February 1, 2006; 66(3): 1473 - 1480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Wright, R. L. Stouffer, and K. D. Rodland High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3688 - 3695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Faedo, C. E. Ford, R. Mehta, K. Blazek, and W. D. Rawlinson Mouse Mammary Tumor-Like Virus Is Associated with p53 Nuclear Accumulation and Progesterone Receptor Positivity but not Estrogen Positivity in Human Female Breast Cancer Clin. Cancer Res., July 1, 2004; 10(13): 4417 - 4419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Vasilevskaya, T. V. Rakitina, and P. J. O'Dwyer Geldanamycin and its 17-Allylamino-17-Demethoxy Analogue Antagonize the Action of Cisplatin in Human Colon Adenocarcinoma Cells: Differential Caspase Activation as a Basis for Interaction Cancer Res., June 15, 2003; 63(12): 3241 - 3246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. H. Chowdhury, M. Radonovich, R. Mahieux, C. Pise-Masison, S. Muralidhar, and J. N. Brady p53 facilitates degradation of human T-cell leukaemia virus type I Tax-binding protein through a proteasome-dependent pathway J. Gen. Virol., April 1, 2003; 84(4): 897 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Braastad, Z. Han, and E. A. Hendrickson Constitutive DNase I Hypersensitivity of p53-Regulated Promoters J. Biol. Chem., February 28, 2003; 278(10): 8261 - 8268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Subramanian and J. D. Griffith Interactions between p53, hMSH2-hMSH6 and HMG I(Y) on Holliday junctions and bulged bases Nucleic Acids Res., June 1, 2002; 30(11): 2427 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Lakhani, M. J. van de Vijver, J. Jacquemier, T. J. Anderson, P. P. Osin, L. McGuffog, and D. F. Easton The Pathology of Familial Breast Cancer: Predictive Value of Immunohistochemical Markers Estrogen Receptor, Progesterone Receptor, HER-2, and p53 in Patients With Mutations in BRCA1 and BRCA2 J. Clin. Oncol., May 1, 2002; 20(9): 2310 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Nicholls, K. G. McLure, M. A. Shields, and P. W. K. Lee Biogenesis of p53 Involves Cotranslational Dimerization of Monomers and Posttranslational Dimerization of Dimers. IMPLICATIONS ON THE DOMINANT NEGATIVE EFFECT J. Biol. Chem., April 5, 2002; 277(15): 12937 - 12945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shan, S. A. Rouhani, H. A. J. Schut, and E. G. Snyderwine 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Modulates Lactogenic Hormone-mediated Differentiation and Gene Expression in HC11 Mouse Mammary Epithelial Cells Cell Growth Differ., December 1, 2001; 12(12): 649 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sivaraman, O. M. Conneely, D. Medina, and B. W. O'Malley p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis PNAS, October 12, 2001; (2001) 221459098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sivaraman, O. M. Conneely, D. Medina, and B. W. O'Malley p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis PNAS, October 23, 2001; 98(22): 12379 - 12384. [Abstract] [Full Text] [PDF]
|
|