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

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 tran- scription 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.

Automated summary

Mre11-Rad50-Xrs2 (MRX) plays a new role in limiting transcription in budding yeast by physically interacting and colocalizing with the transcriptional co-regulator Mediator on chromatin. MRX restricts transcription of coding and noncoding DNA by tethering transcriptionally active loci to the nuclear pore complex (NPC), promoting gene-NPC interactions, contributing to chromosome folding, and controlling gene expression. These findings suggest a distinct role for MRX in transcription and chromosome organization apart from its known function in DNA repair.