DNA damage causally contributes to cancer development and tissue degeneration with aging.(1) Cellular DNA damage responses (DDR) mediate cell cycle arrest to allow time for DNA repair, or induce cellular senescence and apoptosis to eliminate damaged cells.(2) In contrast to cell-autonomous DNA damage responses, it remains less clear how organisms respond to genome instability in certain cell types and how distinct tissues interact when responding to tissue-specific DNA damage. C. elegans comprises an intriguing system to study the interaction between distinct tissues as germ cells evoke conserved DDR mechanisms, while somatic tissues are highly radio resistant.(3) (,) (4) The recent discovery of the "germline DNA damage-induced systemic stress response" (GDISR) sheds new light on non-cell autonomous responses to genome instability.(5) GDISR is mediated by ERK MAP kinase MPK-1 induced putative secreted peptides that are associated with innate immunity. The innate immune response leads to activation of the ubiquitin-proteasome-system (UPS) in somatic tissues, which confers systemic stress resistance. We discuss the role of the innate immunity in mediating systemic DNA damage responses and how UPS activity promotes endurance of somatic tissues.
Keywords: C. elegans; DNA damage response; Innate immunity; aging; stress resistance.