Holliday junctions are efficiently cleaved either by GEN1 endonuclease or the SLX-MUS complex, composed of the SLX1A:SLX4 heterodimer and the heterodimer of MUS81 and EME1 (or, possibly, EME2). Both SLX1A:SLX4 and MUS1:EME1,EME2 possess endonucleolytic activity and act in a coordinated fashion. SLX1A:SLX4 cleaves the double Holliday junction first, which is followed by MUS81:EME1 (or MUS81:EME2) mediated cleavage of the incised Holliday junction. Cleavage by both GEN1 and SLX-MUS predominantly leads to exchange of genetic material between sister chromatids, creating crossover products (Wyatt et al. 2013, Sarbajna et al. 2014).