Multiple functions of MutS- and MutL-related heterocomplexes.

H complexes of MutSand 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 MutLrelated 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 MutSand MutL-related heterodimeric complexes and mispaired bases to other types of DNA structures formed during replication, recombination, and repair.