title: Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer.
abstract: To investigate the role of the presumed DNA mismatch repair (MMR) gene Msh2 in genome stability and tumorigenesis, we have generated cells and mice that are deficient for the gene. Msh2-deficient cells have lost mismatch binding and have acquired microsatellite instability, a mutator phenotype, and tolerance to methylating agents. Moreover, in these cells, homologous recombination has lost dependence on complete identity between interacting DNA sequences, suggesting that Msh2 is involved in safeguarding the genome from promiscuous recombination. Msh2-deficient mice display no major abnormalities, but a significant fraction develops lymphomas at an early age. Thus, Msh2 is involved in MMR, controlling several aspects of genome stability; loss of MMR-controlled genome stability predisposes to cancer.
authors.affiliation: Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam.
authors.forename: N
authors.initials: N
authors.lastname: de Wind
authors.forename: M
authors.initials: M
authors.lastname: Dekker
authors.forename: A
authors.initials: A
authors.lastname: Berns
authors.forename: M
authors.initials: M
authors.lastname: Radman
authors.forename: H
authors.initials: H
authors.lastname: te Riele
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002678:Chimera; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins; D020022:Genetic Predisposition to Disease; D008223:Lymphoma / Q000235:genetics*; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009838:Oligodeoxyribonucleotides; D008769:Methylnitronitrosoguanidine; D004247:DNA; D051718:MutS Homolog 2 Protein