title: Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for microsatellite stability and maintenance of genome integrity.
abstract: Mismatch repair genes are important in maintaining the fidelity of DNA replication. To determine the function of the Caenorhabditis elegans homologue of the MSH2 mismatch repair gene (msh-2), we isolated a strain of C. elegans with an insertion of the transposable element Tc1 within msh-2. Early-passage msh-2 mutants were similar to wild-type worms with regard to lifespan and meiotic chromosome segregation but had slightly reduced fertility. The mutant worms had reduced DNA damage-induced germ-line apoptosis after genotoxic stress. The msh-2 mutants also had elevated levels of microsatellite instability and increased rates of reversion of the dominant unc-58(e665) mutation. In addition, serially passaged cultures of msh-2 worms died out much more quickly than those of wild-type worms. These results demonstrate that msh-2 function in C. elegans is important in regulating both short- and long-term genomic stability.
authors.affiliation: Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599-3280, USA.
authors.forename: Natasha P
authors.initials: NP
authors.lastname: Degtyareva
authors.forename: Patricia
authors.initials: P
authors.lastname: Greenwell
authors.forename: E Randal
authors.initials: ER
authors.lastname: Hofmann
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hengartner
authors.forename: Lijia
authors.initials: L
authors.lastname: Zhang
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Culotti
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Petes
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D020137:Base Pair Mismatch; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D005799:Genes, Dominant; D016678:Genome; D006801:Humans; D008540:Meiosis; D018895:Microsatellite Repeats; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011518:Proto-Oncogene Proteins; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C450145:msh-2 protein, C elegans; D004247:DNA; C497172:MSH2 protein, human; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein