The entanglement of DNA damage and pattern recognition receptor signaling

Cells are under constant pressure to suppress DNA damage originating from both exogenous and endogenous sources. Cellular responses to DNA damage help to prevent mutagenesis and cell death that arises when DNA damage is either left unrepaired or repaired inaccurately. During the "acute phase" of DNA damage signaling, lesions are recognized, processed, and repaired to restore the primary DNA sequence whilst cell cycle checkpoints delay mitotic progression, cell death and the propagation of errors to daughter cells. Increasingly, there is recognition of a "chronic phase" of DNA damage signaling, exemplified by the secretion of dozens of cytokines days after the inciting damage event. In this review, we focus on the cellular origin of these chronic responses, the molecular pathways that control them and the increasing appreciation for the interconnection between acute and chronic DNA damage responses.