Misregulation of R-loop homeostasis promotes genomic instability is associated with progressive neurodegenerative disorders or cancer. Moreover, their presence has biological relevance in regulating gene expression and specialized rearrangement events. A homeostasis emerges from the constant formation and removal of R-loops throughout the genome. This form carries more stability than dsDNA and must be enzymatically resolved in order to restore the native double helix. Structurally, the hybrid adopts an intermediate conformation between B-form double-stranded (ds)DNA and Aform dsRNA. As RNA polymerase progresses along the DNA double helix, newly transcribed RNA threads back to hybridize with the transiently accessible template strand and displace the non-template strand. One such structure, known as an R-loop, occurs during transcription ( Figure 1). Unwinding of the DNA double helix provides access for polymerase to a template strand, and creates torsional stress that can manifest anomalous formation of “non-traditional” moieties. This review covers recent understandings of the molecular basis for R-loop formation, removal, and biological outcomes in the context of cellular stress.Ī variety of topological, structural and hybridization events occur during DNA replication and gene transcription. As accumulation of R-loops is associated with disease, targeting molecular pathways that regulate their formation or removal could provide new avenues for therapeutic intervention. New methodologies and models are being developed to delineate the biology of R-loops, including those related to cell stress-based diseases like cancer. However, they also exist as a form of stress, particularly when replication forks collide with the transcription machinery. In vivo regulatory functions have evolved from R-loops, including regulation of gene expression and telomere lengthening. These hybrids nucleate from guanine rich clusters in the template strand and extend across GC rich spans of transcribed genes. Interestingly, specific DNA-RNA hybrids, known as R-loops, form during transcription and exist in homeostasis throughout the genomes of prokaryotes and eukaryotes. Cells manage this exposure by using topoisomerases and helicases to reduce the inherent topological stress that arises from unwinding the double helix and by coating ssDNA with protective protein complexes. Read more with Noam Ross’s blog post on vectorization.Exposure of genomic, single-stranded DNA (ssDNA) during transcription and replication creates opportunities for the formation of inappropriate secondary structures. On the contrary, for vectorized functions, these questions must be answered only once, which saves a lot of time. These questions must be answered for each iteration, which takes time. Here, the vectorized function is much faster than the two others and the for-loop approach is faster than the sapply equivalent when just-in-time compilation is enabled.Īs an interpreted language, for each iteration res <- x + y, R has to ask:Ĭan I add these two types? what is the type of x + y then?Ĭan I store this result in res or do I need to convert it?