Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems
Figure 6
A schematic representation of models for MMR pathways in E. coli and mutH-less bacteria. (a) - and -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 -methyl-directed MMR, one of the - 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 - exonucleases (exonuclease I (ExoI; PDB ID: 1FXX) and exonuclease X (ExoX)) is responsible for the - 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 - and -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 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 subunit, DNA ligase, and T. thermophilus RecJ.
