A schematic representation of MMR pathway models. (a) Eukaryotic MMR. A DNA mismatch is generated by the misincorporation of a base during DNA replication. recognizes base-base mismatches and nicks the - or -side of the mismatched base on the discontinuous strand. The resulting DNA segment is excised by the EXO1 exonuclease, in cooperation with the single-stranded DNA-binding protein RPA. The DNA strand is resynthesized by DNA polymerase and DNA ligase 1. (b) MMR in mutH-less bacteria. Mismatched bases are recognized by MutS. After the incision of discontinuous strand by MutL, the error-containing DNA strand is removed by the cooperative functions of DNA helicases, such as UvrD, the exonucleases RecJ and ExoI, and the single-stranded DNA-binding protein SSB. DNA polymerase III and DNA ligase fill the gap to complete the repair. (c) E. coli MMR. MutS recognizes mismatched bases, and MutL interacts with and stabilizes the complex. Then, MutH endonuclease is activated to incise the unmethylated GATC site to create an entry point for the excision reaction. DNA helicase, a single-stranded DNA-binding protein, and several exonucleases are involved in the excision reaction. PDB IDs of crystal structures in this figure are 2O8B (human ), 1H7S (human ), 1L1O (human RPA), 3IAY (human DNA polymerase ), 1X9N (human DNA ligase 1), 1E3M (bacterial MutS), 1B63 (bacterial MutL), 2AZO (E. coli MutH), 2ISI (bacterial UvrD), 2ZXO (bacterial RecJ), 3C95 (bacterial ExoI), 2CWA (bacterial SSB), 2HQA (bacterial DNA polymerase III), and 2OWO (bacterial DNA ligase).
