Following generation of a DSB (step 1) the Mre11–Rad50 (M/R) complex is recruited at the site of damage (step 2). While the ancestral SbcC/SbcD Mre11/Rad50 complex of the archaea and bacteria is bipartite, the eukaryotic complex utilizes a third component Nbs1(Xrs2) that is not conserved in archaeal species. Initial processing at the break frequently utilizes the nucleolytic activity of Mre11, which in eukaryotes is potentiated by CtIP(Sae2). During generation of the 3′ single-stranded tails required for the strand invasion step during homologous recombination, the M/R complex facilitates the recruitment of the long-range end-resection machinery at the processed DNA-end. Bacteria use the RecBCD or AddAB, or AdnAB complexes to perform this resection, while in the archaea, this is performed by the HerA–NurA helicase/nuclease complex, while the RecQ family helicases such as BLM(Sgs1) or WRN and the Dna2 or Exo1 nucleases operate in eukaryotic cells (step 3). Unwound strands of the DNA duplex are coated by the single-stranded binding protein (SSB/RPA), which is displaced by the Rad51/RadA/RecA recombinase protein on the resultant 3′ single-stranded proteo-filament (step 4), which then invades the DNA duplex on the homologous chromosome to mediate the homologous recombination-driven repair event. The M/R complex also likely plays important architectural roles during the repair event, including tethering of the homologous chromosomes.