Table 1.
MMR proteins in E. coli, S. cerevisiae and H. sapiens
| E. coli | S. cerevisiae | H. sapiens | Comments |
|---|---|---|---|
| MutS-MutS | Msh2-Msh6 (MutSα) Msh2-Msh3 (MutSβ) |
Msh2-Msh6 (MutSα) Msh2-Msh3 (MutSβ) |
Mispair recognition complex—homodimer in E. coli and a heterodimer in eukaryotes. MutSα and MutSβ have overlapping mispair recognition specificity and are partially redundant |
| Mlh1-Pms1 (MutLα) | Mlh1-Pms2 (MutLα) | Homodimer in E. coli and heterodimer in eukaryotes. MutL (E. coli) and MutLα (eukaryotes) play a central role during MMR. In E. coli, MutL promote the nicking reaction via MutH, whereas in eukaryotes MutLα possess an intrinsic endonuclease activity | |
| MutL-MutL | Mlh1-Mlh2 (MutLβ) | Mlh1-Pms1 (MutLβ) | MutLβ is an accessory factor for MMR |
| Mlh1-Mlh3 (MutLγ) | Mlh1-Mlh3 (MutLγ) | MutLγ substitutes for MutLα in the repair of a minor fraction of mispairs, but primarily acts in the resolution of meiotic recombination intermediates | |
| Dam methylase | Absent | Absent | Promotes N6-adenine methylation at d(GATC) sites, serves as strand discrimination signal in E. coli |
| MutH | Absenta | Absenta | Endonuclease, nicks daughter strand using d(GATC) hemi-methylated sites as strand discrimination signal |
| none | Exo1 | Exo1 | 5′-3′ dsDNA exonuclease, acts in the excision reaction |
| RecJ, ExoVII | None | None | 5′-3′ ssDNA exonuclease, acts in the excision reaction |
| ExoI, ExoVII, ExoX | None | None | 3′-5′ ssDNA exonuclease, acts in the excision reaction |
| UvrD | None or unknown | None or unknown | DNA helicase II, promotes excision reaction, activated by MutS |
| β-clamp | PCNA | PCNA | DNA polymerase processivity factor. In eukaryotes stimulates Mutα endonuclease activity. The gene encoding PCNA in S. cerevisiae is POL30 |
| γ-Complex | RFC | RFC | Loading of β-clamp/PCNA |
| SSB | RPA1-3 | RPA1-3 | ssDNA binding protein, acts in the excision and DNA resynthesis reactions. The genes encoding RPA subunits in S. cerevisiae are RFA1, 2 and, 3 |
| DNA Pol III | Polδ | Pol delta | DNA polymerase that acts in the gap-filling step |
| DNA ligase | Unknown | Ligase I | Seals nicks after DNA resynthesis |
a
This endonuclease function appears to be present in MutLα and MutLγ