Multiple functions of MutS- and MutL-related heterocomplexes

Heterodimeric complexes of MutS- and MutL-related proteins were identified from studies of DNA mismatch repair (MMR) and have been implicated in processing of recombination intermediates. In a recent issue of PNAS, Wang et al. (1) have reported several observations about the function of MutL-related genes of the yeast Saccharomyces cerevisiae in MMR and recombination in meiosis. First, they have observed that MLH1 is the common subunit in three different MutL-related heterodimeric complexes, MLH1–PMS1, MLH1–MLH2, and MLH1–MLH3. Second, a possible role of MLH1–MLH2 in MMR was detected. Third, and most striking, MLH1–MLH3 was shown to play an important role in promoting crossing-over. This last observation extends the eukaryotic paradigm of combinatorial interactions between MutS- and MutL-related heterodimeric complexes and mispaired bases to other types of DNA structures formed during replication, recombination, and repair.