Cleavage of the exposed ssDNA strand of R-loops by structure-specific endonucleases such as xeroderma pigmentosum group F (XPF, also known as ERCC4), xeroderma pigmentosum group G (XPG, also known as ERCC5) and FEN1 (Cristini et al., 2019; Sollier et al., 2014), or by activation-induced cytidine deaminase (AID, also known as AICDA) (Su and Freudenreich, 2017), can cause DNA damage, GIN and accumulation of pro-inflammatory cytosolic nucleic acids in non-S phase and post-mitotic cells (Cristini et al., 2019, 2022; Crossley et al., 2023). This evidence concerns the gene FEN1 and xeroderma pigmentosum-Cockayne syndrome complex.