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.