MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as a heterodimer with MSH2

The process of post-replicative DNA-mismatch repair seems to be highly evolutionarily conserved. In Escherichia coli, DNA mismatches are recognized by the MutS protein [1,2]. Homologues of the E. coli mutS and mutL mismatch-repair genes have been identified in other prokaryotes, as well as in yeast and mammals (see [3] for review). Recombinant Saccharomyces cerevisiae MSH2 (MSH for MutS homologue) [4] and human hMSH2 proteins [5,6] have been shown to bind to mismatch-containing DNA in vitro. However, the physiological role of hMSH2 is unclear, as shown by the recent finding that the mismatch-binding factor hMutS alpha isolated from extracts of human cells is a heterodimer of hMSH2 and another member of the MSH family, GTBP [7,8]. It has been reported that S. cerevisiae possesses a mismatch-binding activity, which most probably contains MSH2 [9]. We show here that, as in human cells, the S. cerevisiae binding factor is composed of MSH2 and a new functional MutS homologue, MSH6, identified by its homology to GTBP.