Abstract
DNA damage is the cause of numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. The DNA damage response (DDR), in turn, coordinates DNA damage checkpoint activation and promotes the removal of DNA lesions. In recent years, several studies have shown how the DDR and the immune system are tightly connected, revealing an important crosstalk between the two of them. This interesting interplay has opened up new perspectives in clinical studies for immunological diseases as well as for cancer treatment. In this review, we provide an overview, from cellular to molecular pathways, on how DDR and the immune system communicate and share the crucial commitment of maintaining the genomic fitness.
Highlights
Genomic integrity and stability are the center upon which cellular survival and homeostasis stand
We provide an overview, from cellular to molecular pathways, on how DNA damage response (DDR) and the immune system communicate and share the crucial commitment of maintaining the genomic fitness
We provide an overview of the agents that cause DNA damage, from solar radiation to DNA-interacting drugs whose effects are likely related to immunological mechanisms
Summary
Genomic integrity and stability are the center upon which cellular survival and homeostasis stand. During DNA synthesis, the replication machinery must overcome numerous obstacles, such as lesions that interfere with fork progression, tightly bound DNA-protein complexes, and non-B form DNA structures (cruciforms, slipped structures, triplexes, G-quadruplexes, Z-DNA, and R loop) [6]. These events can lead to replication stress by stalling of the replication fork, followed by collapse or breakage [7,8]. At the origin of replication stress, multiple mechanisms are involved, including nucleotide pool imbalance, conflict between replication and transcription, and oncogene activation [7,8] We attempted to merge the complexity of different strategies currently employed in the clinic and that stand at the intersection between DDR and immunity
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