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Caenorhabditis elegans DNA Mismatch Repair Gene msh-2 Is Required for Microsatellite Stability and Maintenance of Genome Integrity
Natasha P. Degtyareva, Patricia Greenwell, E. Randal Hofmann, Michael O. Hengartner, Lijia Zhang, Joseph G. Culotti and Thomas D. Petes
Proceedings of the National Academy of Sciences of the United States of America
Vol. 99, No. 4 (Feb. 19, 2002), pp. 2158-2163
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3057935
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2002 National Academy of Sciences