Integration of the DNA Damage Response with Innate Immune Pathways

Abstract

Genotoxic or replicative stress triggers a DNA damage response (DDR) that induces cell cycle arrest, DNA repair or – if the damage is too severe – apoptosis. The DDR has been suggested to represent a barrier against tumorigenesis by preventing the uncontrolled proliferation of cells with genomic instability or harmful mutations. Recent studies have uncovered novel links of the DDR to innate immune signaling pathways. The activation of NF-κB in response to DNA damage is mediated by ATM (ataxia telangiectasia mutated)dependent phosphorylation of NEMO, resulting in the induction of the classical NF-κB pathways. Furthermore links between the DDR and various members of the type I interferon (IFN) pathway have been uncovered. The DDR also increases the sensitivity of cells to immune cell-mediated killing by inducing the expression of surface ligands for activating immune receptors. Here, we review how the DDR links to innate immune pathways and the potential role of these interactions in cancer and viral infection.