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Wagner, C.B.* ; Longaretti, M.* ; Sergi, S.G.* ; Singh, N.* ; Tsirkas, I. ; Bento, F.* ; Wong, R.P.* ; Wilkens, M.* ; Hamperl, S. ; Butter, F.* ; Aharoni, A.* ; Ulrich, H.D.* ; Luke, B.*

Rad53 regulates RNase H1, which promotes DNA replication through sites of transcription-replication conflict.

Cell Rep. 44:116565 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
RNA-DNA hybrids and R-loops can lead to extensive DNA damage and loss of genomic integrity if not regulated in a timely manner. Although RNase H1 overexpression is frequently used as a tool to resolve R-loops, the regulation of RNase H1, overexpressed or endogenous, remains poorly characterized. We reveal that in yeast, overexpressed RNase H1 (RNH1) has no effect on gene expression, cell growth, or RNA-DNA hybrid resolution in wild-type cells. Overexpressed RNase H1 does, however, remove RNA-DNA hybrids in mutants where hybrids have become dysregulated. Endogenous RNase H1 becomes up-regulated and chromatin-associated in the absence of Sen1 in a DNA replication checkpoint-dependent manner. Rnh1 gets recruited to genomic loci where RNA-DNA hybrids accumulate following the loss of Sen1. Rnh1, together with Sen1, promotes DNA replication at sites of transcription-replication conflict. Hence, RNase H1, overexpressed or endogenous, responds to unscheduled, stress-inducing RNA-DNA hybrids.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cp: Molecular Biology ; R-loop ; Rna-dna Hybrid ; Rnase H1 ; Rnh1 ; Sen1 ; Senataxin; Polymerase-ii; Rna/dna Hybrids; Gene-expression; R-loops; Genome; Sen1; Termination; System; Roles; H2
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 44, Heft: 11, Seiten: , Artikelnummer: 116565 Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)
Förderungen European Research Council (ERC)

DFG
German Research Foundation (DFG)
Helmholtz Association
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)