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"RNA:DNA hybrid formation has a dark side. Abundant literature suggests that accumulation of long and stable RNA:DNA hybrids could be harmful to the cells predisposing genomes to breakages and rearrangements. Persistent hybrids can be generated by RNA invasion into a homologous DNA duplex, which exposes the non-complementary single-stranded DNA (ssDNA) strand leading to the formation of a structure called the R-loop. R-loops form during DNA transcription when the nascent RNA has the chance to anneal to the DNA template behind the transcribing RNA polymerase (RNAP) or even to a distant locus containing a homologous DNA sequence. While the formation of R-loops is a physiological step in transcription, their improper turnover and/or unscheduled formation can interfere with DNA replication thus contributing to the phenomenon of replication stress. More recently, RNA:DNA hybrids and/or R-loops have been observed at DNA double-strand breaks (DSBs) where they promote DNA repair. However, if not timely removed, hybrids trigger inaccurate DSB repair pathways, leading to genome instability.Many excellent reviews have summarized the vast literature on R-loops that has grown exponentially in the last decades.Here we highlight the recent progress made in understanding the mechanisms that lead to R-loop/RNA:DNA hybrid formation and their impact on genome instability due to the interference with DNA replication and DSB repair. Moreover, we will discuss how the aberrant regulation of RNA:DNA hybrid turnover may impact on human health, taking as a paradigm the dysfunctions associated with the RNA/DNA helicase Senataxin.RNA:DNA hybrids are the most abundant non-B DNA structures in the genomes of many organisms, including humans. RNA:DNA hybrids associated with R-loops affect not only on gene expression, but also on genome stability. Thus, not surprisingly, recent experimental investigations suggest a strong link between the disruption of R-loop metabolism and different human degenerative disorders [142]. The growing list of factors implicated in human diseases and directly involved in R-loop/RNA:DNA hybrid" … Again, do you TRUST the WHO, CDC, NIH, Fauci, Gates, Governments, et al.to be able to ALTER YOUR DNA?In the replies will be references...