title: Caenorhabditis elegans EXO-3 contributes to longevity and reproduction: differential roles in somatic cells and germ cells.
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 oxidative base damage. This result suggested that the major substrate of EXO-3 in the gonad was 3' blocking end generated by NTH-1, and that EXO-3 played an important role in reproduction. A contribution of EXO-3 to reproduction was also suggested by our finding here that the decrease of self-brood size of the exo-3 mutant became more marked when worms were treated with methyl methanesulfonate (MMS) and sodium bisulfite (NaHSO3). This study demonstrated differential roles of EXO-3 in somatic cells and germ cells.
authors.affiliation: Laboratory of Stress Response Biology, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Stress Response Biology, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Moriwaki
authors.affiliation: Laboratory of Stress Response Biology, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Funakoshi
authors.affiliation: Laboratory of Stress Response Biology, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan. Electronic address: qmzhang@kingyo.zool.kyoto-u.ac.jp.
authors.forename: Qiu-Mei
authors.initials: QM
authors.lastname: Zhang-Akiyama
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005854:Germ Cells / Q000166:cytology / Q000201:enzymology*; D006066:Gonads / Q000166:cytology / Q000201:enzymology*; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D012098:Reproduction / Q000187:drug effects / Q000235:genetics; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D009153:Mutagens; D008741:Methyl Methanesulfonate; D004720:Endonucleases; D045647:DNA Glycosylases; C553373:NTH-1 protein, C elegans; D051981:Uracil-DNA Glycosidase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C504039:EXO-3 protein, C elegans
keywords: AP endonuclease; AP site; C. elegans; EXO-3; Longevity; Reproduction