Zatreanu, DianaHan, ZhongMitter, RichardTumini, EmanuelaWilliams, Hannah C.Gregersen, Lea HaarupDirac-Svejstrup, A. BarbaraRoma, StefaniaStewart, AengusAguilera López, AndrésSvejstrup, Jesper2019-12-042019-12-042019Zatreanu, D., Han, Z., Mitter, R., Tumini, E., Williams, H.C., Gregersen, L.H.,...,Svejstrup, J. (2019). Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability. Molecular Cell, 76 (1), 57-69.e9.1097-27651097-4164https://hdl.handle.net/11441/90721Although correlations between RNA polymerase II (RNAPII) transcription stress, R-loops, and genome instability have been established, the mechanisms underlying these connections remain poorly understood. Here, we used a mutant version of the transcription elongation factor TFIIS (TFIISmut), aiming to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. Indeed, TFIISmut expression results in slower elongation rates, relative depletion of polymerases from the end of genes, and increased levels of stopped RNAPII; it affects mRNA splicing and termination as well. Remarkably, TFIISmut expression also dramatically increases R-loops, which may form at the anterior end of backtracked RNAPII and trigger genome instability, including DNA strand breaks. These results shed light on the relationship between transcription stress and R-loops and suggest that different classes of R-loops may exist, potentially with distinct consequences for genome stability.application/pdfengAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/53BP1BacktrackingDNA-RNA hybridsR-loopsRNA polymerase IITFIISTranscript cleavageTranscript elongationTranscription-associated genome instabilityinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1016/j.molcel.2019.07.037