R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response.

ABSTRACT: R-loops are RNA-DNA-hybrid-containing nucleic acids with important cellular roles. Deregulation of R-loop dynamics can lead to DNA damage and genome instability¹, which has been linked to the action of endonucleases such as XPG^2-4. However, the mechanisms and cellular consequences of such processing have remained unclear. Here we identify a new population of RNA-DNA hybrids in the cytoplasm that are R-loop-processing products. When nuclear R-loops were perturbed by depleting the RNA-DNA helicase senataxin (SETX) or the breast cancer gene BRCA1 (refs. ^5-7), we observed XPG- and XPF-dependent cytoplasmic hybrid formation. We identify their source as a subset of stable, overlapping nuclear hybrids with a specific nucleotide signature. Cytoplasmic hybrids bind

SUBMITTER: Crossley MP 

PROVIDER: S-EPMC9949885 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature