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 reviewpeer-review

    94 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

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