Unusual RNA/DNA Structures and Genome Stability in Health and Disease

R-loops are unusual nucleic acid structures composed of an RNA/DNA hybrid and ssDNA which arise during the process of transcription in all living organisms. These structures have been implicated in many important biological processes, including DNA replication, transcription, epigenetics and generation of antibody diversity. More recently, R-loops have been associated with neurodegenerative diseases and cancer promoting genome instability in these disorders. However, the molecular mechanisms underlying biological or pathological functions of R-loops are currently not well understood. With the aim to address this question our lab have recently established unbiased proteomic approach using S9.6 antibody which specifically recognises RNA/DNA hybrids to uncover proteins that interact with R-loops in human cells (R-loop interactome) (Cristini et al 2018). We have employed this powerful resource to reveal the function of R-loops in genome stability and generation of R-loop-mediated dsDNA breaks during transcription. Furthermore, we will also present our work on pathological R-loops associated with neurodegenerative diseases and demonstrate the power of R-loop interactome in uncovering the molecular players of mechanisms underlying human disease.