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. Author manuscript; available in PMC: 2022 Oct 1.
Published in final edited form as: DNA Repair (Amst). 2021 Jul 17;106:103182. doi: 10.1016/j.dnarep.2021.103182

Figure 2. Pause-associated R-loops as candidate harmful R-loops.

Figure 2.

A. Schematic of a gene and its hypothetical R-loop formation state in 10 independent chromosomes. Class I R-loops are suggested to frequently arise at promoters as a result of promoter-proximal pausing. By contrast, elongation-associated Class II R-loops are spread throughout the gene body and therefore occur at much lower frequencies at any given site. RNA is only depicted when in a R-loop bound state or exiting RNAP (full transcript not shown). B. Under pathological conditions caused for instance by defective mRNA processing, RNAPII pausing is proposed to increase, causing a focal increase in Class I R-loops. Class II R-loops are by contrast proposed to be reduced as a result of lower transcription initiation due to increased pausing. Under such conditions, paused RNAPII complexes anchored to Class I R-loops may represent significant obstacles to replication fork progression, causing DNA damage.