Elongation factor TFIIS prevents transcription stress and R-loop accumulation to maintain genome stability
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Diana Zatreanu Zhong Han Richard Mitter Emanuela Tumini Hannah Williams Lea Gregersen Barbara Dirac-Svejstrup Stefania Roma Aengus Stewart Andres Aguilera Jesper SvejstrupAbstract
Although 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 (TFIIS), aiming to specifically induce increased levels of RNAPII pausing, arrest, and/or backtracking in human cells. Indeed, TFIIS 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, TFIIS 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.
Journal details
Journal Molecular Cell
Volume 76
Issue number 1
Pages 57-69.e9
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.molcel.2019.07.037
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Europe PubMed Central 31519522
Pubmed 31519522