DNA, if damaged, cannot be replaced. If not replaceable, it must be repaired. The so-called “DNA damage response” (DDR) is a coordinate set of evolutionary conserved events that arrest the cell-cycle (DNA damage checkpoint function) in proliferating cells and attempts DNA repair. Until DNA damage has not been repaired in full, cell proliferation is not resumed in normal cells.DNA damage is a physiological event. Ageing and cancer are both associated with DNA damage accumulation. In the past, we contribute to better understand the mechanisms and the consequences of DNA damage generation and DDR activation in both settings.We have recently identified a completely hitherto undiscovered level of control of DDR activation, so far considered a proteinaceous only signaling cascade. We have discovered that short RNA species are detectable at DNA damage sites and are necessary for DDR activation at DNA lesions. These RNA species are generated by an evolutionary-conserved RNA processing machinery. However, they serve purposes never reported before.We believe that our findings change radically our understanding of DDR modulation in mammals and disclose a fertile unspoilt ground for exciting investigations.