title: The DNA damage response and immune signaling alliance: Is it good or bad? Nature decides when and where.
abstract: The characteristic feature of healthy living organisms is the preservation of homeostasis. Compelling evidence highlight that the DNA damage response and repair (DDR/R) and immune response (ImmR) signaling networks work together favoring the harmonized function of (multi)cellular organisms. DNA and RNA viruses activate the DDR/R machinery in the host cells both directly and indirectly. Activation of DDR/R in turn favors the immunogenicity of the incipient cell. Hence, stimulation of DDR/R by exogenous or endogenous insults triggers innate and adaptive ImmR. The immunogenic properties of ionizing radiation, a prototypic DDR/R inducer, serve as suitable examples of how DDR/R stimulation alerts host immunity. Thus, critical cellular danger signals stimulate defense at the systemic level and vice versa. Disruption of DDR/R-ImmR cross talk compromises (multi)cellular integrity, leading to cell-cycle-related and immune defects. The emerging DDR/R-ImmR concept opens up a new avenue of therapeutic options, recalling the Hippocrates quote "everything in excess is opposed by nature."
authors.affiliation: Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Pateras
authors.affiliation: Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Havaki
authors.affiliation: Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Xenia
authors.initials: X
authors.lastname: Nikitopoulou
authors.affiliation: Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Vougas
authors.affiliation: Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, UK; Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Townsend
authors.affiliation: School of Life Sciences, Heriot Watt University, Edinburgh, UK.
authors.forename: Michalis I
authors.initials: MI
authors.lastname: Panayiotidis
authors.affiliation: School of Applied Mathematical & Physical Sciences, National Technical University of Athens, Zografou 15780, Greece.
authors.forename: Alexandros G
authors.initials: AG
authors.lastname: Georgakilas
authors.affiliation: Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece; Biomedical Research Foundation, Academy of Athens, Athens, Greece; Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, UK; Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: vgorg@med.uoa.gr.
authors.forename: Vassilis G
authors.initials: VG
authors.lastname: Gorgoulis
mesh_terms: D004249:DNA Damage / Q000276:immunology*; D004260:DNA Repair / Q000276:immunology*; D004266:DNA Virus Infections / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D012327:RNA Virus Infections / Q000276:immunology; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53
keywords: Autoimmunity; Cancer; DNA damage response and repair machinery; Immune response; Inflammation; Pattern recognition receptors