The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer

Richard Fishel, Mary Kay Lescoe, M. R S Rao, Neal G. Copeland, Nancy A. Jenkins, Judy Garber, Michael Kane, Richard Kolodner

Research output: Contribution to journalArticle

2474 Scopus citations

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 2p22-21 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.

Original languageEnglish (US)
Pages (from-to)1027-1038
Number of pages12
JournalCell
Volume75
Issue number5
DOIs
StatePublished - Dec 3 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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