Theyeast genome encodes four proteins (Pms1 and Mlh1-3) homologous to the bacterial mismatch repair component, MutL. These proteins can form three types of complexes; Mlh1 is the common component of all three complexes, interacting with Pms1, Mlh2, and Mlh3. Four mammalian MutL homologues also exist. The principal heterodimers that function in mitotic repair and meiotic reciprocal recombination are Mlh1-Pms2 (Pms1 in yeast) and Mlh1-Mlh3, respectively [, , ].This entry represents Mlh3 and its homologues from eukaryotes. Mlh3 is involved in DNA mismatch repair, correcting insertion-deletion loops resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. It is a component of the MutL-beta heterodimer (a heterodimer of Mlh1 and Mlh3), which probably forms a ternary complex with the MutS-beta heterodimer that initially recognises the DNA mismatches. Mlh3 plays a major role in promoting meiotic crossing-over and is involved in maintaining the genetic stability of simple sequence repeats by correction of frameshift intermediates [, , ].
Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through replication errors during homologous recombination and as a result of DNA damage. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex []. This entry represents a family of evolutionarily related DNA mismatch repair proteins, including MutL, Mlh1, Mlh2 and Mlh3, and Pms 1 and 2. Bacterial MutL proteins are homodimers, while their eukaryotic homologues form heterodimers consisting of the MutL homologue Mlh1 and either Pms1, Pms2 or Mlh3 [, ]. MutL homologues share a conserved ATP binding site [].
This entry represents the N-terminal domain of DNA mismatch repair proteins, such asMutL. Bacterial MutL proteins are homodimers, while their eukaryotic homologues form heterodimers consisting of the MutL homologue Mlh1 and either Pms1, Pms2 or Mlh3 [, ]. MutL proteins and their homologues share sequence homology at their N termini over the first 300-400 residues; the C termini are less well conserved, they constitute the main dimerization domain and are required for interaction between MutL and UvrD helicase []. The activity of the protein is modulated by the ATP-dependent dimerization of the N-terminal domain [].The dimeric MutL protein has a key function in communicating mismatch recognition by MutS to downstream repair processes. Mismatch repair contributes to the overall fidelity of DNA replication by targeting mispaired bases that arise through replication errors during homologous recombination and as a result of DNA damage. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex [].
Mismatch repair is one of five major DNA repair pathways, the others being homologous recombination repair, non-homologous end joining, nucleotide excision repair, and base excision repair. The mismatch repair system recognises and repairs mispaired or unpaired nucleotides that result from errors in DNA replication. Many proteins involved in the different repair processes also play a role in apoptosis when DNA damage is excessive, thereby helping to prevent carcinogenesis []. The mismatch repair protein, Mlh1 (mutL homologue 1), has a dual role in DNA repair and apoptosis. Mlh1 acts as a heterodimer in conjunction with Pms2, Pms1 (post-meiotic segregation 1 and 2) or Mlh3 (MutL homologue 3), which function as adaptor proteins that link Msh (MutS homologue) heterodimers to the DNA repair machinery, resulting in excision and repair of the mispaired base [].This entry represents the mismatch repair protein MutL.
