The crosstalk between DNA damage response components and DNA-sensing innate immune signaling pathways.

When DDR factors are defective or cytosolic DNA degradation enzymes are functionally mutated, aberrant DNAs will accumulate in the nucleus or the cytosol and be recognized by DNA sensors to trigger immune signaling activation. The DDR components RAD51 and RPA could bind to short nuclear ssDNA fragments, thereby preventing ssDNA's cytosolic leakage from inducing cGAS-dependent IFN-I activation [[29]]. Different DNA sensors recognize DNA depending on the structural features of the DNA ligands (circular or linear), the localization (in the nucleus or the cytoplasm), the source (damaged DNA or virus DNA), and the length of the DNA fragment. DNA damage accumulates gradually during genotoxic stress of replication, ionizing radiation, chemical regent, and virus infection, leading to the persistent activation of DNA damage sensors and the DNA damage responses (DDR). [Extracted from the article]