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 rec ognized 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 Sacc haromyces 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 b y the recent finding that the mismatch-binding factor hMutS alpha isol ated from extracts of human cells is a heterodimer of hMSH2 and anothe r member of the MSH family, GTBP [7,8]. It has been reported that S. c erevisiae possesses a mismatch-binding activity, which most probably c ontains MSH2 [9]. We show here that, as in human cells, the S. cerevis iae binding factor is composed of MSH2 and a new functional MutS homol ogue, MSH6, identified by its homology to GTBP.