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. It restricts transcription of coding and noncoding DNA independently by a mechanism that does not require the nuclease activity of Mre11. MRX is required to tether the active GAL locus to the nuclear pore complex (NPC) and 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. NGS-based analysis of Rad50, Mlp1 (ChIP-seq). Chromosome folding with MicroC-XL. Analysis of gene expression by strand specific, total RNA-seq of G1 synchronised S. cerevisiae cells, wild type and mutants for the MRX complex and degradation pathways.