Targeted gene disruption of the Caenorhabditis elegans L-isoaspartyl protein repair methyltransferase impairs survival of dauer stage nematodes

Archives of Biochemistry and Biophysics
R M KaganS Clarke

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

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Citations

Sep 6, 2008·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Kelley L BanfieldPamela L Larsen
Oct 25, 2011·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Robert J Shmookler ReisRobert R Delongchamp
Jan 20, 2009·Biochimica Et Biophysica Acta·Evgenia V Megalou, Nektarios Tavernarakis
Dec 26, 2006·Developmental Biology·Tara A GomezSteven G Clarke
Dec 24, 2018·The Journal of Biological Chemistry·Liang Yin, Caroline S Harwood
Apr 26, 2014·The Journal of Biological Chemistry·Alexander N PatanananSteven G Clarke
Nov 28, 2020·The Biochemical Journal·Nitin Uttam Kamble, Manoj Majee
Apr 7, 1999·Archives of Biochemistry and Biophysics·A Niewmierzycka, S Clarke
Nov 5, 1999·Gene·B GöttgensA R Green
Nov 4, 2008·Mechanisms of Ageing and Development·Tara A GomezSteven G Clarke

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