Factors that act in heteroduplex rejection and MMR. (A) Heteroduplex rejection and MMR are both initiated by Msh heterodimers binding to DNA mismatches, but subsequent steps involve interactions with different sets of factors. (B) Model for heteroduplex rejection during SSA involving Msh proteins and the Sgs1-Top3-Rmi1 complex. Following strand annealing, Msh proteins bind to mismatches (red star) in heteroduplex DNA and undergo a conformational change that, in the left panel, licenses recruitment of Sgs1-Top3-Rmi1, loaded at the junction between the heteroduplex and the 3′ nonhomologous tail, to promote heteroduplex rejection. In the right panel, recruitment of nonhomologous tail removal factors instead of Sgs1-Top3-Rmi1, results in the removal of the 3′ nonhomologous tail, followed by MMR. Adapted from George and Alani (2012).