Figure 4.

Strand excision and resynthesis during DNA mismatch repair. (A) Mismatch repair is bidirectional with MutS and MutL molecules loaded both 5′ and 3′ to the mismatch. Consequently, strand incision can occur on both sides of the mismatch. (B) When strand incision is 5′ of the mismatch then the helicase and polymerase work in the same direction. The helicase processivity is enhanced by the C-terminal domain of MutL, while the polymerase follows the excision. (C) The displaced strand is removed by an exonuclease until shortly after the mismatch where without the aid of MutL, the helicase lacks processivity and terminates strand removal. (D) When the incision occurs 3′ to the mismatch, the polymerase moves opposite to the direction of the helicase and is therefore blocked by MutL that is bound to the 3′ resected end of the newly synthesised strand. (E) UvrD associates with the C-terminal domain of MutL that increases the processivity of the helicase. (F) An exonuclease removes the displaced strand up to shortly after the mismatch, followed by (G) resynthesis of the excised strand.