QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mallette, F. A. Articles by Ferbeyre, G. Search for Related Content PubMed PubMed Citation Articles by Mallette, F. A. Articles by Ferbeyre, G. Related Content Related Article Social Bookmarking                   What's this?

RESEARCH COMMUNICATION

The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence

Département de Biochimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada

Here we report that RNA interference against ATM inhibited p53 accumulation in cells expressing oncogenic STAT5 and cooperated with Rb inactivation to suppress STAT5A-induced senescence. Knocking down ATM was also effective to bypass E2F1-induced senescence and in combination with Rb inactivation, inhibited RasV12-induced senescence. Cells that senesced in response to ca-STAT5A or RasV12 accumulated DNA damage foci and activated ATM, ATR, Chk1, and Chk2, indicating that aberrant oncogene activation induces a DNA damage signaling response. Intriguingly, bypassing oncogene-induced senescence by inactivation of p53 and Rb did not eliminate the accumulation of oncogene-induced DNA damage foci (ODDI), suggesting a mechanism that may limit transformation in immortalized cells.

[Keywords: STAT5; RasV12; E2F1; ATM; DNA damage; p53; senescence]

Received August 29, 2006; revised version accepted November 15, 2006.

E-MAIL g.ferbeyre{at}umontreal.ca; FAX (514) 343-2210.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1487307

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Oncogenes and senescence: breaking down in the fast lane

Michael T. Hemann and Masashi Narita
Genes & Dev. 2007 21: 1-5. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				C. A Schmitt In vivo Complexities of Cellular Senescence in Tumor Development and Therapy Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 499 - 504. [Abstract] [Full Text] [PDF]

				D. A. Lewis, Q. Yi, J. B. Travers, and D. F Spandau UVB-induced Senescence in Human Keratinocytes Requires a Functional Insulin-like Growth Factor-1 Receptor and p53 Mol. Biol. Cell, April 1, 2008; 19(4): 1346 - 1353. [Abstract] [Full Text] [PDF]

				M. Xu, Q. Yu, R. Subrahmanyam, M. J. Difilippantonio, T. Ried, and J. M. Sen {beta}-Catenin Expression Results in p53-Independent DNA Damage and Oncogene-Induced Senescence in Prelymphomagenic Thymocytes In Vivo Mol. Cell. Biol., March 1, 2008; 28(5): 1713 - 1723. [Abstract] [Full Text] [PDF]

				M. Tardat, R. Murr, Z. Herceg, C. Sardet, and E. Julien PR-Set7 dependent lysine methylation ensures genome replication and stability through S phase J. Cell Biol., December 31, 2007; 179(7): 1413 - 1426. [Abstract] [Full Text] [PDF]

				M. Stagno D'Alcontres, A. Mendez-Bermudez, J. L. Foxon, N. J. Royle, and P. Salomoni Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA J. Cell Biol., December 3, 2007; 179(5): 855 - 867. [Abstract] [Full Text] [PDF]

				J.-H. Chen, C. N. Hales, and S. E. Ozanne DNA damage, cellular senescence and organismal ageing: causal or correlative? Nucleic Acids Res., December 3, 2007; 35(22): 7417 - 7428. [Abstract] [Full Text] [PDF]

				F. Rodier, J. Campisi, and D. Bhaumik Two faces of p53: aging and tumor suppression Nucleic Acids Res., December 3, 2007; 35(22): 7475 - 7484. [Abstract] [Full Text] [PDF]

				F. A. Mallette, M.-F. Gaumont-Leclerc, G. Huot, and G. Ferbeyre Myc Down-regulation as a Mechanism to Activate the Rb Pathway in STAT5A-induced Senescence J. Biol. Chem., November 30, 2007; 282(48): 34938 - 34944. [Abstract] [Full Text] [PDF]

				M. Reimann, C. Loddenkemper, C. Rudolph, I. Schildhauer, B. Teichmann, H. Stein, B. Schlegelberger, B. Dorken, and C. A. Schmitt The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo Blood, October 15, 2007; 110(8): 2996 - 3004. [Abstract] [Full Text] [PDF]

				E. H. Heiss, Y. D. C. Schilder, and V. M. Dirsch Chronic Treatment with Resveratrol Induces Redox Stress- and Ataxia Telangiectasia-mutated (ATM)-dependent Senescence in p53-positive Cancer Cells J. Biol. Chem., September 14, 2007; 282(37): 26759 - 26766. [Abstract] [Full Text] [PDF]

				C. Hafner, E. Lopez-Knowles, N. M. Luis, A. Toll, E. Baselga, A. Fernandez-Casado, S. Hernandez, A. Ribe, T. Mentzel, R. Stoehr, et al. Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern PNAS, August 14, 2007; 104(33): 13450 - 13454. [Abstract] [Full Text] [PDF]

				A. Marusyk, L. J. Wheeler, C. K. Mathews, and J. DeGregori p53 Mediates Senescence-Like Arrest Induced by Chronic Replicational Stress Mol. Cell. Biol., August 1, 2007; 27(15): 5336 - 5351. [Abstract] [Full Text] [PDF]