Carcinogenesis, Vol. 23, No. 6, 1025-1032,
June 2002
© 2002 Oxford University Press
CARCINOGENESIS |
The onset of p53-dependent DNA repair or apoptosis is determined by the level of accumulated damaged DNA
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
The p53 tumor suppressor gene plays an important role in both apoptosis and DNA repair pathways that are pivotal for genomic stability. Here we show that the treatment of cells with low doses of 
-irradiation or cisplatin resulted in an immediate enhancement of p53-dependent DNA repair, measured by base excision repair (BER) activity. However, treatment of cells with high doses of DNA damaging agents resulted in a reduction in p53-dependent DNA repair and in the induction of p53-dependent apoptosis. Analysis of p53 upstream molecular events suggested that regulation of p53-associated DNA repair is ATM-dependent. Furthermore, we observed that while dephosphorylation of Ser376 at the C-terminus of the p53 protein was associated with enhancement in DNA repair, phosphorylation at the N-terminal Ser15 resulted in the reduction in DNA repair. The latter is also in correlation with an enhancement in the specific DNA binding activity and in the induction of apoptosis. Treatment of cells with a caspase inhibitor, prior to the damaging agent-blocked apoptosis, had no effect on the DNA repair pattern. Taken together, this suggests that the decision of cells to induce a p53-dependent DNA repair or apoptosis is most probably controlled by the level of genotoxic agent introduced to cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. K. Singh, R. Kumar, A. Sharma, R. Arora, R. Chawla, S. K. Jain, and R. K. Sharma Podophyllum hexandrum Fraction (REC-2006) Shows Higher Radioprotective Efficacy in the p53-Carrying Hepatoma Cell Line: A Role of Cell Cycle Regulatory Proteins Integr Cancer Ther, September 1, 2009; 8(3): 261 - 272. [Abstract] [PDF]
|
|
|
|
 |
|
 S. N. Kassam and A. J. Rainbow UV-inducible base excision repair of oxidative damaged DNA in human cells Mutagenesis, January 1, 2009; 24(1): 75 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Devlin, P. C. Mack, R. A. Burich, P. H. Gumerlock, H.-J. Kung, M. Mudryj, and R. W. deVere White Impairment of the DNA Repair and Growth Arrest Pathways by p53R2 Silencing Enhances DNA Damage-Induced Apoptosis in a p53-Dependent Manner in Prostate Cancer Cells Mol. Cancer Res., May 1, 2008; 6(5): 808 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Laumonier, J. Segers, S. Laurent, A. Michel, F. Coppee, A. Belayew, L. V. Elst, and R. N. Muller A New Peptidic Vector for Molecular Imaging of Apoptosis, Identified by Phage Display Technology J Biomol Screen, August 1, 2006; 11(5): 537 - 545. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Sugo, N. Niimi, Y. Aratani, K. Takiguchi-Hayashi, and H. Koyama p53 Deficiency Rescues Neuronal Apoptosis but Not Differentiation in DNA Polymerase {beta}-Deficient Mice Mol. Cell. Biol., November 1, 2004; 24(21): 9470 - 9477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Zurer, L. J. Hofseth, Y. Cohen, M. Xu-Welliver, S. P. Hussain, C. C. Harris, and V. Rotter The role of p53 in base excision repair following genotoxic stress Carcinogenesis, January 1, 2004; 25(1): 11 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. MacGregor The Future of Regulatory Toxicology: Impact of the Biotechnology Revolution Toxicol. Sci., October 1, 2003; 75(2): 236 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, Y. Yu, H. E. Hamrick, and P. J. Duerksen-Hughes ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses Carcinogenesis, October 1, 2003; 24(10): 1571 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ansah and N. J. Gooderham The Popular Herbal Antimalarial, Extract of Cryptolepis sanguinolenta, Is Potently Cytotoxic Toxicol. Sci., December 1, 2002; 70(2): 245 - 251. [Abstract] [Full Text] [PDF]
|
|