RT Journal Article
T1 Elongation Factor TFIIS Prevents Transcription Stress and R-Loop Accumulation to Maintain Genome Stability.
A1 Zatreanu, Diana
A1 Han, Zhong
A1 Mitter, Richard
A1 Tumini, Emanuela
A1 Williams, Hannah
A1 Gregersen, Lea
A1 Dirac-Svejstrup, A Barbara
A1 Roma, Stefania
A1 Stewart, Aengus
A1 Aguilera, Andres
A1 Svejstrup, Jesper Q
K1 53BP1
K1 DNA-RNA hybrids
K1 R-loops
K1 RNA polymerase II
K1 TFIIS
K1 backtracking
K1 transcript cleavage
K1 transcript elongation
K1 transcription-associated genome instability
AB 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.
YR 2019
FD 2019-09-10
LK http://hdl.handle.net/10668/14507
UL http://hdl.handle.net/10668/14507
LA en
DS RISalud
RD Apr 6, 2025