Abstract:
We have identified a human homolog of the bacterial
MutS and S. cerevisiae MSH proteins, called hMSH2.
Expression of hMSH2 in E. coli causes a dominant mutator
phenotype, suggesting that hMSH2, like other
divergent MutS homologs, interferes with the normal
bacterial mismatch repair pathway. hMSH2 maps to
human chromosome 2~22-21 near a locus implicated
in hereditary nonpolyposis colon cancer (HNPCC). A
T to C transition mutation has been detected in the
-6 position of a splice acceptor site in sporadic colon
tumors and in affected individuals of two small HNPCC
kindreds. These data and reports indicating that S. cerevisiae
msh2 mutations cause an instability of dinucleotide
repeats like those associated with HNPCC suggest
that hMSH2 is the HNPCC gene.
