FIGURE 2.
Summary of DSB formation and repair in mammals. SPO11 and associated factors including REC114, MEI4, MEI1, and IHO1 generate a double strand break to initiate recombination. Endonuclease activity results in cleavage of a small DNA fragment associated with SPO11. The resulting single-stranded DNA overhang is extended on both DNA strands by exonuclease activity. RAD51 and DMC1 along with other proteins aid in strand invasion of the homologous chromosome to begin the process of homologous recombination to repair the DSB. This forms the D-loop on the homolog that is extended by HFM1. If the other side of the DSB is “captured” a double Holliday junction is formed and stabilized by MSH4 and MSH5. This can either resolve to a crossover or a non-crossover with RNF212, HEI10, and CNTD1 involved in regulating crossover selection. Resolution to the final crossover products is promoted by MLH1, MLH3, and EXO1.