Sustained activation of DNA damage response in irradiated apoptosis-resistant cells induces reversible senescence associated with mTOR downregulation and expression of stem cell markers.

Cells respond to genotoxic stress by activating the DNA damage response (DDR). When injury is severe or irreparable, cells induce apoptosis or cellular senescence to prevent transmission of the lesions to the daughter cells upon cell division. Resistance to apoptosis is a hallmark of cancer that challenges the efficacy of cancer therapy.

An integrated approach for monitoring cell senescence.

Cellular senescence is considered as a crucial mechanism of tumor suppression that helps to prevent the growth of cells at risk for neoplastic transformation. In normal cells, cellular senescence induces an irreversible cell cycle arrest in response to telomere dysfunction, oncogene activation, genotoxic stress and a persistent DNA damage response (DDR). This process is accompanied by dramatic changes in cell morphology as well as in the activity of several signaling pathways.