RRC ID 53328
著者 Kato Y, Miyaji M, Zhang-Akiyama QM.
タイトル FUdR extends the lifespan of the short-lived AP endonuclease mutant in Caenorhabditis elegans in a fertility-dependent manner.
ジャーナル Genes Genet Syst
Abstract The anticancer drug 5-fluorouracil (5-FU) and its metabolite 5-fluoro-2'-deoxyuridine (FUdR) inhibit thymidylate synthase and induce uracil bases in DNA. FUdR is commonly used for inhibiting fertility when measuring the lifespan of the nematode Caenorhabditis elegans. However, it is not known whether DNA damage induced by FUdR affects lifespan. EXO-3 is an apurinic/apyrimidinic endonuclease in C. elegans, and we reported previously that deletion of the exo-3 gene causes reproductive abnormalities and decreased lifespan. In this study, we found that FUdR extended the lifespan of exo-3 mutants. We measured the lifespan of multiple germline mutants to examine whether this lifespan extension effect was dependent on fertility. In the presence of a fem-1 mutation, which causes a deficiency in sperm production, FUdR did not extend the lifespan of the exo-3 mutant. In glp-1 mutants, which do not develop gonads, the exo-3 mutant was not short-lived, and FUdR did not extend its lifespan. These results suggest that the lifespan extension effect of FUdR depends on fertility and the presence of gonads. fem-3 mutants, which do not produce oocytes, had increased lifespan in the presence of FUdR, independent of the exo-3 mutation. It is possible that the fem-3 mutant was susceptible to the lifespan extension effect of FUdR. From these results, we suggest that FUdR affects the lifespan of C. elegans in two ways: by interfering with fertility, which extends lifespan, and by inducing DNA base damage, which reduces lifespan.
巻・号 91(4)
ページ 201-207
公開日 2017-3-17
DOI 10.1266/ggs.15-00064
PMID 27582048
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Cell Cycle Proteins / genetics DNA Damage* DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics* Deoxyuridine / analogs & derivatives* Deoxyuridine / pharmacology Female Fertility / drug effects* Gene Expression Regulation / drug effects Male Mutation Oocytes / drug effects Receptors, Notch / genetics Spermatozoa / drug effects
IF 0.917
引用数 5
リソース情報
線虫 tm4374