Mre11Rad50Xrs2

Mre11-Rad50-Xrs2, commonly referred to as the MRX complex, is a conserved heterotrimeric protein assembly in the budding yeast Saccharomyces cerevisiae that plays a central role in the detection, processing, and signaling of DNA double-strand breaks. It is the functional counterpart of the mammalian MRN complex (Mre11-Rad50-Nbs1), with Xrs2 serving as the Nbs1 homolog in yeast.

The complex comprises three subunits: Mre11, a nuclease that provides endonuclease and exonuclease activities; Rad50, an ATPase with long coiled-coil domains that tether and bridge DNA ends; and Xrs2, a regulatory subunit that facilitates nuclear localization and mediates interactions with checkpoint signaling components, including the Tel1 kinase (the yeast ATM homolog). The MRX complex localizes rapidly to DSBs and acts to stabilize broken ends, recruit other repair factors, and initiate end processing.

In DNA repair, MRX participates in the initial end processing required for homologous recombination. It makes a cut near the break and, in cooperation with Sae2 (CtIP in vertebrates), begins resection to generate 3' single-stranded DNA overhangs. This processing lays the groundwork for extensive resection by other nucleases such as Exo1 or the Sgs1-Dna2 pathway. MRX also contributes to checkpoint signaling by promoting activation of Tel1/ATM and to the maintenance of telomeres, where it helps prevent unwanted end-joining and genomic instability.

Mutations in MRE11, RAD50, or XRS2 lead to sensitivity to ionizing radiation and defects in DSB repair and telomere maintenance, underscoring the MRX complex’s essential role in genome stability. The complex is highly conserved, highlighting its fundamental function across eukaryotes.