Budding yeast Mus81 complexes with Mms4 (EME1 or EME2 in humans) to form a structure-specific endonuclease that targets branched DNA structures with a 5'-end at the branch nick [, ]. Its typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions [, ].Similar to MUS81-EME1, human MUS81-EME2 cleaves 3'-flaps, replication forks and nicked Holliday junctions, and exhibits limited endonuclease activity with intact Holliday junctions. However, MUS81-EME2 can also cleave a variety of DNA structures including D-loop recombination intermediates and nicked duplex [, ].
