Mus81

Mus81 is a conserved endonuclease found in eukaryotes and archaea that plays a crucial role in DNA repair and replication. It is a member of the Mus81-Mms4/Eme1 protein family, which are characterized by their distinct structure and nuclease activity. Mus81 typically functions as a heterodimer with Mms4 in yeast or Eme1 in metazoans. This complex is a Holliday junction resolvase, meaning it can cleave branched DNA structures that arise during DNA replication and recombination. These branched structures, such as Holliday junctions and replication fork stalling intermediates, can be toxic to cells if not resolved properly, leading to genomic instability and cell death.

The Mus81-Mms4/Eme1 complex is known to resolve a variety of DNA structures, including replication forks that have become stalled or collapsed. This resolution is vital for allowing replication to proceed or for processing stalled forks into structures that can be repaired. Mus81 also participates in the repair of DNA double-strand breaks, particularly through homologous recombination pathways. Its precise roles and the specific DNA structures it targets can vary somewhat between different organisms, reflecting evolutionary adaptations. Dysregulation or deficiency of Mus81 activity has been linked to increased susceptibility to DNA damaging agents and can contribute to various forms of cancer.