Triage in medical situations refers to the assignment of degrees of urgency to wounds or illnesses to decide the order of treatment of a large number of patients or casualties. Radiation injury for the cell can be considered as a major “wound to its crucial organs” and in many cases a matter of life or death. The delineation of how DDR exerts immune responses still can be considered as a puzzling topic . Based on the above ideas, it is generally accepted that once complex and/or persistent DNA damage is induced and most probably GI, immune signaling is initiated by different components of the DDR/R pathway including DNA damage sensors, transducer kinases, effectors and repair proteins . In general, association between innate immune system response and persistent DNA damage has been shown in various cases as reviewed in . In the same direction, Ermolaeva et al. used the nematode Caenorhabditis elegans eukaryotic system to show that DNA damage in germ cells induces an innate immune response that consequently leads to activation of the ubiquitin-proteasome system (UPS) in somatic tissues, which confers enhanced proteostasis and systemic stress resistance . Rodier et al. have shown that X-ray damaged human HCA2 fibroblasts develop persistent chromatin lesions bearing DSBs detected using γH2AX/53BP1 foci as surrogate markers, which triggers the secretion of inflammatory cytokines such as interleukin-6 (IL-6) . It is important to notice, that this cytokine secretion occurred only after establishment of persistent and heavy DNA damage (10 Gy of X-rays), associated with senescence and not after transient DNA damage responses (X-ray dose of 0.5 Gy). On the other hand, systemic DNA damage responses are part of the organism’s defense system in order to secure removal of damaged and malfunctioning cells and preserve tissue integrity and functionality i.e., tissue homeostasis . For example, it has been shown that in repair deficient Ataxia-telangiectasia (AT) patients, where the repair protein ATM is defective, small DNA fragments generated from the excessive DNA-breaks accumulate in the cytoplasm of these patients' cells. The DNA fragments are consequently recognized by innate immune receptors that normally detect viral DNA. This “false alarm” of viral invasion results in the production of type I interferon which in turn drives the innate immune system into an activated state .