DNA mismatch recognition and binding in human cells has been thought t
o be mediated by the hMSH2 protein. Here it is shown that the mismatch
-binding factor consists of two distinct proteins, the 100-kilodalton
hMSH2 and a 160-kilodalton polypeptide, GTBP (for G/T binding protein)
. Sequence analysis identified GTBP as a new member of the MutS homolo
g family. Both proteins are required for mismatch-specific binding, a
result consistent with the finding that tumor-derived cell lines devoi
d of either protein are also devoid of mismatch-binding activity.