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A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization.

Molecular cell (2020-12-06)
Romain Forey, Antoine Barthe, Mireille Tittel-Elmer, Maxime Wery, Marie-Bénédicte Barrault, Cécile Ducrot, Andrew Seeber, Nils Krietenstein, Ugo Szachnowski, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Jennifer A Cobb, Oliver J Rando, Julie Soutourina, Michel Werner, Karine Dubrana, Susan M Gasser, Antonin Morillon, Philippe Pasero, Armelle Lengronne, Jérôme Poli
ABSTRACT

Mre11-Rad50-Xrs2 (MRX) is a highly conserved complex with key roles in various aspects of DNA repair. Here, we report a new function for MRX in limiting transcription in budding yeast. We show that MRX interacts physically and colocalizes on chromatin with the transcriptional co-regulator Mediator. MRX restricts transcription of coding and noncoding DNA by a mechanism that does not require the nuclease activity of Mre11. MRX is required to tether transcriptionally active loci to the nuclear pore complex (NPC), and it also promotes large-scale gene-NPC interactions. Moreover, MRX-mediated chromatin anchoring to the NPC contributes to chromosome folding and helps to control gene expression. Together, these findings indicate that MRX has a role in transcription and chromosome organization that is distinct from its known function in DNA repair.

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