The MRN complex (MRE11:RAD50:NBS1:CtIP) endoncleolytically cleaves a single strand of DNA 3' to SPO11 attached to a double strand break.
SPO11 forms a dimer and each subunit cleaves a single strand of DNA, thus creating a double-strand break. After cleaving DNA, a SPO11 subunit remains covalently attached to each 5' end via a tyrosine residue. SPO11 is removed from the DNA by cleavage and exonucleolytic digestion of single strands 3' to the attached SPO11. The overall products are a resected 5' end (protruding 3' overhang) and a covalent complex of SPO11 with an oligonucleotide. Two size classes of oligonucleotide are observed: 12 to 26 nucleotides and 28 to 34 nucleotides. The enzyme responsible for excision of SPO11:oligonucleotide in mammals is inferred to be MRE11 in the MRE11:RAD50:NBS1:CtIP complex based on conservation of the reaction mechanism across yeast, plants, and animals (Sartori et al. 2007).
In fission and budding yeast the Mre11:Rad50:Xrs2/Nbs1 (MRN/MRX) complex is required for removal of SPO11. In human somatic cells the MRN complex together with CtIP resects double-strand breaks but the role of the MRN complex in mammalian meiosis, though essential, is unclear (Sartori et al. 2007).
After excision of SPO11:oligonucleotide the recessed 5' end is further resected by unknown exonucleases.