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

Pharmacol Ther

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:

Published: October 2015

AI Article Synopsis

  • Healthy organisms maintain homeostasis through coordinated DNA damage response/recovery (DDR/R) and immune response (ImmR) systems that work together to support cellular function.
  • DNA and RNA viruses trigger these DDR/R mechanisms, enhancing immunogenicity in host cells and leading to a stronger immune response against threats.
  • Disruption in the communication between DDR/R and ImmR can lead to cellular and immune system weaknesses, highlighting potential new therapeutic strategies based on this relationship.

Article 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."

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http://dx.doi.org/10.1016/j.pharmthera.2015.06.011DOI Listing

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