The DNA damage response and immune signaling alliance: Is it good or bad? Nature decides when and where

Ioannis S. Pateras, Sophia Havaki, Xenia Nikitopoulou, Konstantinos Vougas, Paul A. Townsend, Mihalis I Panagiotidis, Alexandros G. Georgakilas, Vassilis G. Gorgoulis

    Research output: Contribution to journalLiterature review

    83 Citations (Scopus)

    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."

    Original languageEnglish
    Pages (from-to)36-56
    Number of pages21
    JournalPharmacology and Therapeutics
    Volume154
    Early online date3 Jul 2015
    DOIs
    Publication statusPublished - Oct 2015

    Keywords

    • DNA damage response and repair machinery
    • Immune response
    • Pattern recognition receptors
    • Inflammation
    • Cancer
    • Autoimmunity
    • NF-KAPPA-B
    • DOUBLE-STRAND BREAKS
    • EPSTEIN-BARR-VIRUS
    • TUMOR-INFILTRATING LYMPHOCYTES
    • SYSTEMIC-LUPUS-ERYTHEMATOSUS
    • ONCOGENE-INDUCED SENESCENCE
    • COMMON FRAGILE SITES
    • REGULATORY T-CELLS
    • HUMAN CANCER-CELLS
    • NOD-LIKE RECEPTORS

    Cite this

    Pateras, I. S., Havaki, S., Nikitopoulou, X., Vougas, K., Townsend, P. A., Panagiotidis, M. I., Georgakilas, A. G., & Gorgoulis, V. G. (2015). The DNA damage response and immune signaling alliance: Is it good or bad? Nature decides when and where. Pharmacology and Therapeutics, 154, 36-56. https://doi.org/10.1016/j.pharmthera.2015.06.011