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Tsirkas, I. ; Lee, C.S.K. ; Dovrat, D.* ; Singh, N.* ; Paleiov, Z.* ; Lalonde, M. ; Sajid, A. ; Straub, T.* ; Sergi, S.G.* ; Bento, F.* ; Luke, B.* ; Aharoni, A.* ; Hamperl, S.

The balance between R-loops and RNAPII occupancy determines the outcome of transcription-replication conflicts.

Nucleic Acids Res. 54:gkag1139 (2026)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Maintaining genome integrity requires the precise coordination of replication and transcription. While R-loops are known to cause transcription-replication conflicts (TRCs), the precise nature of the barrier, whether it is the RNA:DNA hybrid itself, the stalled RNA Polymerase II (RNAPII), or a combination of both, remains elusive. Using live-cell imaging in yeast to monitor a single R-loop prone locus in real time, we demonstrate that wild-type replisomes traverse R-loop enriched transcription units with high efficiency. We find that while R-loops initially repress transcription, replisome passage prompts a robust recovery of transcription activity. Indeed, we discover that R-loops serve a critical regulatory function by suppressing excessive RNAPII occupancy. In an RNAPII mutant with high DNA affinity, the enzymatic removal of R-loops leads to a pile-up of RNAPII molecules, creating a barrier to replication, more severe than the R-loops themselves. Thus, our findings reveal a dual nature of R-loops: while they can be obstacles and repress transcription, they can also serve as a physiological buffer that prevents the formation of high-density RNAPII 'trains'. These findings establish that the precise regulation of both R-loop levels and RNAPII density is critical for preventing harmful TRCs and maintaining genome stability.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Zeitschrift Nucleic Acids Research
Quellenangaben Band: 54, Heft: 21, Seiten: , Artikelnummer: gkag1139 Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)