Figure 1.

A general outline for mammalian MMR. MMR begins with the binding of MutSα or MutSβ heterodimers to the distorted segment of mispaired DNA. MutSα and MutSβ are composed of MSH2 and MSH6 or MSH3, respectively. Primary recognition by the MutSα complex is best for 1–2 base mismatches whereas unpaired loops of 3–4 bases preferentially recruit MutSβ. The MutLα dimer of PMS2 and MLH1 then joins the MutS-DNA complex for secondary recognition and eventual repair and resolution. In the absence of PMS2, MMR is therefore generally deficient. The proliferating cell nuclear antigen (PCNA) associated with MLH1 may catalyze MMR by stimulating nuclease activity and facilitating removal of the mismatch. (Adapted from ref. 9.)