%0 Journal Article
%A Zatreanu, Diana
%A Han, Zhong
%A Mitter, Richard
%A Tumini, Emanuela
%A Williams, Hannah
%A Gregersen, Lea
%A Dirac-Svejstrup, A Barbara
%A Roma, Stefania
%A Stewart, Aengus
%A Aguilera, Andres
%A Svejstrup, Jesper Q
%T Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability.
%D 2019
%U http://hdl.handle.net/10668/14507
%X 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 (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.
%K 53BP1
%K DNA-RNA hybrids
%K R-loops
%K RNA polymerase II
%K TFIIS
%K backtracking
%K transcript cleavage
%K transcript elongation
%K transcription-associated genome instability
%~