A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype.

Journal Article (Journal Article)

Defects in mismatch repair (MMR) genes result in a mutator phenotype by inducing microsatellite instability (MI), a characteristic of hereditary nonpolyposis colorectal cancers (HNPCC) and a subset of sporadic colon tumors. Present models describing the mechanism by which germ line mutations in MMR genes predispose kindreds to HNPCC suggest a "two-hit" inactivation of both alleles of a particular MMR gene. Here we present experimental evidence that a nonsense mutation at codon 134 of the hPMS2 gene is sufficient to reduce MMR and induce MI in cells containing a wild-type hPMS2 allele. These results have significant implications for understanding the relationship between mutagenesis and carcinogenesis and the ability to generate mammalian cells with mutator phenotypes.

Full Text

Duke Authors

Cited Authors

  • Nicolaides, NC; Littman, SJ; Modrich, P; Kinzler, KW; Vogelstein, B

Published Date

  • March 1, 1998

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 1635 - 1641

PubMed ID

  • 9488480

Pubmed Central ID

  • PMC108878

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.18.3.1635


  • eng

Conference Location

  • United States