10779/crick.11619840.v1
Diana Zatreanu
Diana
Zatreanu
Zhong Han
Zhong
Han
Richard Mitter
Richard
Mitter
Emanuela Tumini
Emanuela
Tumini
Hannah Williams
Hannah
Williams
Lea Gregersen
Lea
Gregersen
A Barbara Dirac-Svejstrup
A Barbara
Dirac-Svejstrup
Stefania Roma
Stefania
Roma
Aengus Stewart
Aengus
Stewart
Andres Aguilera
Andres
Aguilera
Jesper Q Svejstrup
Jesper Q
Svejstrup
Elongation factor TFIIS prevents transcription stress and R-loop accumulation to maintain genome stability
The Francis Crick Institute
2020
53BP1
DNA-RNA hybrids
R-loops
RNA polymerase II
TFIIS
backtracking
transcript cleavage
transcript elongation
transcription-associated genome instability
Svejstrup FC001166
AS-ack
PRT-ack
HTS-ack
CB
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
2020-01-15 16:53:55
Journal contribution
https://crick.figshare.com/articles/journal_contribution/Elongation_factor_TFIIS_prevents_transcription_stress_and_R-loop_accumulation_to_maintain_genome_stability/11619840
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.