Systemic DNA damage responses: organismal adaptations to genome instability.
DNA damage checkpoints are important tumor-suppressor mechanisms that halt cell cycle progression to allow time for DNA repair, or induce senescence and apoptosis to remove damaged cells permanently. Non-cell-autonomous DNA damage responses activate the innate immune system in multiple metazoan species. These responses not only enable clearance of damaged cells and contribute to tissue remodeling and regeneration but can also result in chronic inflammation and tissue damage. Germline DNA damage-induced systemic stress resistance (GDISR) is mediated by an ancestral innate immune response and results in organismal adjustments to the presence of damaged cells. We discuss GDISR as an organismal DNA damage checkpoint mechanism through which elevated somatic endurance can extend reproductive lifespan when germ cells require extended time for restoring genome stability.
Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, 50674 Cologne, Germany.
Maria A
MA
Ermolaeva
Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Genetics, University of Cologne, Zülpicher Strasse 47a, 50674 Cologne, Germany; Systems Biology of Ageing Cologne, University of Cologne, 50937 Cologne, Germany. Electronic address: bjoern.schumacher@uni-koeln.de.
Björn
B
Schumacher
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D004249:DNA Damage; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D012038:Regeneration / Q000235:genetics
DNA damage induced systemic stress resistance (GDISR); DNA damage response (DDR); DNA repair; aging; immune response; inflammation; innate immunity; tissue repair