MUS81-EME1 endonuclease complex (MUS81-EME1)

The MUS81-EME1 endonuclease complex is a structure-specific nuclease essential for processing DNA intermediates during replication and repair. It consists of the catalytic subunit MUS81 and the regulatory subunit EME1, which together recognize and cleave branched DNA structures like Holliday junctions and stalled replication forks (UniProt Q96NY9, Q8N163). This activity is particularly vital during the late G2 and M phases of the cell cycle, where it facilitates the resolution of recombination intermediates and supports mitotic DNA synthesis (MiDAS) at difficult-to-replicate regions (PubMed: 26371554). In the context of oncology, the complex is a key target for synthetic lethality strategies. Cancer cells with deficiencies in the homologous recombination pathway, such as those with BRCA1 or BRCA2 mutations, become highly dependent on MUS81-EME1 for survival (PubMed: 30639243). Consequently, small molecule inhibitors of MUS81 are being explored to selectively induce DNA damage and apoptosis in these vulnerable tumor cells while sparing healthy tissue. Beyond direct inhibition, the complex is also studied for its role in mediating resistance to certain chemotherapeutic agents that induce replication stress.

Other names

MUS81-EME1 structure-specific endonucleaseEME1-MUS81 complexMMS4-MUS81 (yeast ortholog)Crossover junction endonuclease MUS81 complex

Inhibition of the structure-specific endonuclease activity to prevent the resolution of stalled replication forks and recombination intermediates, inducing synthetic lethality in DNA repair-deficient cells.