Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for microsatellite stability and maintenance of genome integrity.
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.
Degtyareva
Natasha P
NP
Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599-3280, USA.
Greenwell
Patricia
P
Hofmann
E Randal
ER
Hengartner
Michael O
MO
Zhang
Lijia
L
Culotti
Joseph G
JG
Petes
Thomas D
TD
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
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