Targeted gene disruption of the Caenorhabditis elegans L-isoaspartyl protein repair methyltransferase impairs survival of dauer stage nematodes
Abstract
The methylation of abnormal L-isoaspartyl residues by protein L-isoaspartate (D-aspartate) O-methyltransferase (EC 2.1.1.77) can lead to their conversion to L-aspartyl residues. For polypeptides damaged by spontaneous reactions that generate L-isoaspartyl residues, these steps represent a protein repair pathway that can limit the accumulation of potentially detrimental proteins in the aging process. We report here the construction and the characterization of an animal model deficient in this methyltransferase. We utilized Tc1-transposon-mediated mutagenesis in the nematode Caenorhabditis elegans to construct a homozygous excision mutant lacking exons 2-5 of the pcm-1 gene encoding this enzyme. Nematodes carrying this deletion exhibited no detectable L-isoaspartyl methyltransferase activity. These worms demonstrated normal morphology and behavior and adult mutant nematodes exhibited a normal lifespan. However, the survival of dauer-phase mutants was diminished by 3.5-fold relative to wild-type dauers after 50 days in the dauer phase. The fitness of the pcm-1 deletion nematodes was reduced by about 16% relative to that of wild-type nematodes as measured by the ability of these mutants to compete reproductively against a wild-type...Continue Reading
References
Site-selected insertion of the transposon Tc1 into a Caenorhabditis elegans myosin light chain gene.
Citations
Non-repair pathways for minimizing protein isoaspartyl damage in the yeast Saccharomyces cerevisiae.
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