R loops: new modulators of genome dynamics and function

José M. Santos-Pereira & Andrés Aguilera, Nature Reviews Genetics (2015) doi:10.1038/nrg3961, Published online 15 September 2015

R loops are also a major threat to genome stability. For this reason, several DNA and RNA metabolism factors prevent R-loop formation in cells. Dysfunction of these factors causes R-loop accumulation, which leads to replication stress, genome instability, chromatin alterations or gene silencing. Importantly, Friedreich ataxia (FRDA) and fragile X syndrome (FXS) occur as a result of repeat expansions in the frataxin (FXN) and fragile X mental retardation 1 (FMR1) genes, respectively; this leads to gene silencing through H3K9me2 deposition on the expanded regions, which thus become fragile. Such expansions accumulate R loops, providing a new link among heterochromatin, R loops and replication-dependent fragility.