Breaking bad: R-loops and genome integrity

•R-loops are dynamic structures that regulate diverse cellular processes.•R-loops threaten genomic and epigenomic stability.•R-loops are associated with cancer and neurodegenerative diseases.

R-loops, nucleic acid structures consisting of an RNA–DNA hybrid and displaced single-stranded (ss) DNA, are ubiquitous in organisms from bacteria to mammals. First described in bacteria where they initiate DNA replication, it now appears that R-loops regulate diverse cellular processes such as gene expression, immunoglobulin (Ig) class switching, and DNA repair. Changes in R-loop regulation induce DNA damage and genome instability, and recently it was shown that R-loops are associated with neurodegenerative disorders. We discuss recent developments in the field; in particular, the regulation and effects of R-loops in cells, their effect on genomic and epigenomic stability, and their potential contribution to the origin of diseases including cancer and neurodegenerative disorders.