Crossover junction endonuclease MUS81-Essential meiotic structure-specific endonuclease 1 complex (MUS81-EME1)

The Crossover junction endonuclease MUS81-Essential meiotic structure-specific endonuclease 1 (MUS81-EME1) complex is a heterodimeric structure-specific endonuclease that plays a pivotal role in DNA repair and the maintenance of genome stability (UniProt: Q96NY9, Q8NBL1). It is primarily responsible for the resolution of branched DNA intermediates, such as Holliday junctions and stalled replication forks, particularly during the late G2 and M phases of the cell cycle (PubMed: 21741376). By cleaving these structures, the complex facilitates the completion of homologous recombination and ensures proper chromosome segregation. In clinical oncology, MUS81-EME1 is a significant target for synthetic lethality strategies, especially in tumors with deficiencies in other DNA repair pathways like BRCA1/2 or ATM (PubMed: 30635538). Inhibition of the complex in these susceptible backgrounds leads to an accumulation of toxic DNA intermediates, resulting in mitotic catastrophe and apoptosis. Current drug discovery efforts are focused on identifying potent small-molecule inhibitors to exploit these vulnerabilities in various cancers, including breast and ovarian malignancies (PubMed: 32884058).

Other names

MUS81-MMS4 complexMUS81-EME1 endonucleaseStructure-specific endonuclease MUS81-EME1

Inhibition of the endonuclease activity of the MUS81-EME1 complex to prevent the resolution of DNA recombination intermediates, leading to synthetic lethality in DNA-repair-deficient cancer cells (PubMed: 30635538).