MUS81EME1

MUS81-EME1 is a structure-specific nuclease complex in eukaryotes formed by the proteins MUS81 and EME1. It cleaves a range of branched DNA structures, most notably Holliday junctions, regressed replication forks, and DNA flaps, contributing to DNA repair and replication fork processing. The nuclease activity generates DNA breaks that are processed by other repair pathways, enabling genome maintenance.

In humans, MUS81 and EME1 form a catalytic heterodimer required for function. The complex is conserved across eukaryotes, with the yeast counterpart Mus81-Mms4. Activity is coordinated within broader nuclease networks, particularly with the SLX4 scaffold, which coordinates multiple structure-specific nucleases including MUS81-EME1 and SLX1-SLX4.

Cell-cycle regulation: MUS81-EME1 activity is upregulated during S and G2 phases and is stimulated in response to replication stress and DNA damage. It participates in the processing of stalled replication forks and in the resolution of recombination intermediates. Loss or reduced activity leads to accumulation of DNA damage and genome instability and increases cellular sensitivity to certain DNA damaging agents.

Clinical and research aspects: The MUS81-EME1 pathway is studied in cancer biology for its role in maintaining genome integrity and its influence on responses to chemotherapeutic agents. As part of the network of structure-specific nucleases, it remains a focus for understanding replication-associated DNA repair and potential therapeutic targeting.