Caenorhabditis elegans EXO-3 contributes to longevity and reproduction: differential roles in somatic cells and germ cells

Mutation Research
Yuichi KatoQiu-Mei Zhang-Akiyama

Abstract

Apurinic/apyrimidinic (AP) sites are the major DNA damage generated continuously even under normal conditions, and inhibit DNA replication/transcription. AP endonucleases are ubiquitous enzymes required for the repair of AP sites and 3' blocking ends, but their physiological roles in multicellular organisms are not fully understood. In this study, we investigated how an AP endonuclease functions in a multicellular organism (Caenorhabditis elegans (C. elegans)). EXO-3 is one of the AP endonucleases in C. elegans. Using an exo-3 mutant worm, we found that deletion of the exo-3 gene caused shortened lifespan in an ung-1-dependent manner. UNG-1 is a uracil DNA glycosylase in C. elegans, and the present finding suggested that UNG-1 is the major producer of AP sites that affects lifespan, and EXO-3 contributes to longevity by completing the repair of uracil. Next we found that the exo-3 gene was abundantly expressed in the gonads, and AP sites in the gonad were efficiently repaired, suggesting that EXO-3 functioned particularly in the gonad. Deletion of the exo-3 gene resulted in a significant decrease in self-brood size. This was rescued by deficiency of NTH-1, which is a bifunctional DNA glycosylase in C. elegans that recognizes ox...Continue Reading

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Citations

Mar 29, 2014·PLoS Genetics·Diana Andrea Fernandes de AbreuQueelim Ch'ng
Apr 5, 2014·PLoS Genetics·David W JohnsonAndrew V Samuelson
May 3, 2011·PLoS Genetics·Sri Devi NarasimhanHeidi A Tissenbaum
Mar 2, 2013·PloS One·Brad T MooreL Ryan Baugh
Jul 9, 2016·Environmental Toxicology and Pharmacology·Soudabeh ImanikiaVolker M Arlt
Sep 29, 2011·Developmental and Comparative Immunology·Jun WangHinrich Schulenburg
Dec 22, 2020·Frontiers in Cell and Developmental Biology·Noha ElsakrmyDindial Ramotar

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