Figure 6: A schematic representation of models for MMR pathways in E. coli and mutH-less bacteria. (a) 5 - and 3 -methyl-directed MMR in E. coli. DNA mismatches principally result from misincorporation of bases during DNA replication. The MutS (PDB ID: 1E3M)/MutL (PDB ID: 1NHJ) complex recognizes a mismatch and activates the MutH endonuclease (PDB ID: 1AZO). MutH nicks the unmethylated strand of the duplex to introduce an entry point for the excision reaction. In 3 -methyl-directed MMR, one of the 5 - 3 exonucleases (RecJ and exonuclease VII (ExoVII)) removes the error-containing DNA strand in cooperation with UvrD helicase (PDB ID: 2IS4) and single-stranded DNA-binding protein (SSB; PDB ID: 1EYG). By contrast, one of the 3 - 5 exonucleases (exonuclease I (ExoI; PDB ID: 1FXX) and exonuclease X (ExoX)) is responsible for the 3 - 5 excision reaction. DNA polymerase III (PDB ID: 2HNH) and DNA ligase (PDB ID: 2OWO) synthesize a new strand to complete the repair. (b) A predicted model for 5 - and 3 -nick-directed MMR in T. thermophilus. After recognition of a mismatch by MutS (TTHA1324), MutL (TTHA1323) incises the discontinuous strand of the mismatched duplex to direct the excision reaction to the newly synthesized strand. The error-containing DNA segment is excised by UvrD helicase (TTHA1427), SSB (TTHA0244), and an exonuclease (either RecJ (TTHA1167; PDB ID: 2ZXR) or ExoI (TTHB178)) followed by the resynthesis of a new strand by DNA polymerase III (TTHA0180) and DNA ligase (TTHA1097). The modeled structures of T. thermophilus MutS, MutL (amino acid residues 1–316), ExoI, DNA polymerase III 𝛼 subunit, DNA ligase, and E. coli RecJ were modeled using SWISS-MODEL. The template structures used for model building were E. coli MutS, the N-terminal domain of MutL, ExoI, UvrD, DNA polymerase III 𝛼 subunit, DNA ligase, and T. thermophilus RecJ.