InterPro domain: IPR028830

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 [ 1 , 2 , 3 ].

The yeast 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 [ 4 , 5 , 5 ].

1. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc. Natl. Acad. Sci. U.S.A. 95, 12404-9
2. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc. Natl. Acad. Sci. U.S.A. 96, 13914-9
3. Reduced meiotic crossovers and delayed prophase I progression in AtMLH3-deficient Arabidopsis. EMBO J. 25, 1315-23
4. Eukaryotic DNA mismatch repair. Curr. Opin. Genet. Dev. 9, 89-96
5. Meiotic recombination intermediates and mismatch repair proteins. Cytogenet. Genome Res. 107, 232-48