title: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics Markey Center for Molecular Genetics University of Vermont Medical School Burlington 05405.
authors.forename: R
authors.initials: R
authors.lastname: Fishel
authors.forename: M K
authors.initials: MK
authors.lastname: Lescoe
authors.forename: M R
authors.initials: MR
authors.lastname: Rao
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: J
authors.initials: J
authors.lastname: Garber
authors.forename: M
authors.initials: M
authors.lastname: Kane
authors.forename: R
authors.initials: R
authors.lastname: Kolodner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012326:RNA Splicing; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein