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FIGURE 5-36 Mismatch excision repair in human cells. The mismatch excision-repair pathway corrects errors introduced during replication. A complex of the MSH2 and MSH6 proteins (bacterial MutS homologs 1 and 6) binds to a mispaired segment of DNA in such a way as to distinguish between the template and the newly synthesized daughter strand (step 1). This binding triggers binding of MLH1 and PMS2 (both homologs of bacterial MutL). The resulting DNA-protein complex then binds an endonuclease that cuts the newly synthesized daughter strand. Next a DNA helicase unwinds the helix, and an exonuclease removes several nucleotides from the cut end of the daughter strand, including the mismatched base (step 2). Finally, as with base excision repair, the gap is filled in by a DNA polymerase (Pol δ, in this case) and sealed by DNA ligase (step 3).