Dissemin is shutting down on January 1st, 2025

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Cold Spring Harbor Laboratory Press, Genes & Development, 1(21), p. 43-48, 2007

DOI: 10.1101/gad.1487307

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

Journal article published in 2007 by Frédérick A. Mallette ORCID, Marie-France Gaumont-Leclerc, Gerardo Ferbeyre ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.