A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes

Abstract Nuclear pore complexes (NPCs) have increasingly recognized interactions with the genome, as exemplified in yeast, where they bind transcribed or damaged chromatin. By combining genome-wide approaches with live imaging of model loci, we uncover a correlation between NPC association and the a...

Full description

Saved in:
Bibliographic Details
Published inNature communications Vol. 14; no. 1; p. 5606
Main Authors Penzo, Arianna, Dubarry, Marion, Brocas, Clémentine, Zheng, Myriam, Mangione, Raphaël M, Rougemaille, Mathieu, Goncalves, Coralie, Lautier, Ophélie, Libri, Domenico, Simon, Marie-Noëlle, Géli, Vincent, Dubrana, Karine, Palancade, Benoit
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 20.09.2023
Nature Publishing Group UK
Nature Portfolio
Subjects
Biochemistry, Molecular Biology
Chromatin
Damage accumulation
Deoxyribonucleic acid
DNA
Genomes
Genomic instability
Genomics
Genotoxicity
Hybridization
Lethality
Life Sciences
Nuclear pores
Proteins
R-loops
Relocation
Replication forks
Tethering
Transcription
Yeasts
Online AccessGet full text

Cover

More Information
Summary:Abstract Nuclear pore complexes (NPCs) have increasingly recognized interactions with the genome, as exemplified in yeast, where they bind transcribed or damaged chromatin. By combining genome-wide approaches with live imaging of model loci, we uncover a correlation between NPC association and the accumulation of R-loops, which are genotoxic structures formed through hybridization of nascent RNAs with their DNA templates. Manipulating hybrid formation demonstrates that R-loop accumulation per se, rather than transcription or R-loop-dependent damages, is the primary trigger for relocation to NPCs. Mechanistically, R-loop-dependent repositioning involves their recognition by the ssDNA-binding protein RPA, and SUMO-dependent interactions with NPC-associated factors. Preventing R-loop-dependent relocation leads to lethality in hybrid-accumulating conditions, while NPC tethering of a model hybrid-prone locus attenuates R-loop-dependent genetic instability. Remarkably, this relocation pathway involves molecular factors similar to those required for the association of stalled replication forks with NPCs, supporting the existence of convergent mechanisms for sensing transcriptional and genotoxic stresses.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-41345-z