Shown are mechanisms by which R-loops may lead to pausing of elongating RNA polymerase II (Pol II) and transcription termination. a. Backtracking may arrest Pol II over the R-loop. Pol II oscillates between transcription elongation and backtracking. The presence of an R-loop may terminate the function of backtracked Pol II. b. During transcription, the R-loop remains fixed relative to the DNA helix, while elongating Pol II continues rotating along the helical path. The nascent transcript produced downstream of the R-loop must therefore wrap around the DNA, which may lead to Pol II arrest due to buildup of torsional stress. c. R-loops can promote the production of double-stranded RNA that recruits the RNase Dicer and the histone methyltransferase G9a, which forms a repressive chromatin environment that promotes Pol II pausing. Conversely, R-loop recognition and dissolving enzymes such as BRCA1, the RNA helicases senataxin (SETX), DHX9 and DDX5, and 5'-3' exoribonuclease 2 (XRN2) are also required for proper transcription termination at certain genes.