FUdR extends the lifespan of the short-lived AP endonuclease mutant in <i>Caenorhabditis elegans</i> in a fertility-dependent manner

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Abstract

<p>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 <i>Caenorhabditis elegans</i>. However, it is not known whether DNA damage induced by FUdR affects lifespan. EXO-3 is an apurinic/apyrimidinic endonuclease in <i>C. elegans</i>, and we reported previously that deletion of the <i>exo-3</i> gene causes reproductive abnormalities and decreased lifespan. In this study, we found that FUdR extended the lifespan of <i>exo-3</i> 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 <i>fem-1</i> mutation, which causes a deficiency in sperm production, FUdR did not extend the lifespan of the <i>exo-3</i> mutant. In <i>glp-1</i> mutants, which do not develop gonads, the <i>exo-3</i> 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. <i>fem-3</i> mutants, which do not produce oocytes, had increased lifespan in the presence of FUdR, independent of the <i>exo-3</i> mutation. It is possible that the <i>fem-3</i> mutant was susceptible to the lifespan extension effect of FUdR. From these results, we suggest that FUdR affects the lifespan of <i>C. elegans</i> in two ways: by interfering with fertility, which extends lifespan, and by inducing DNA base damage, which reduces lifespan.</p>

Journal

  • Genes & Genetic Systems

    Genes & Genetic Systems 91(4), 201-207, 2016

    The Genetics Society of Japan

Codes

  • NII Article ID (NAID)
    130005450122
  • NII NACSIS-CAT ID (NCID)
    AA11077421
  • Text Lang
    ENG
  • ISSN
    1341-7568
  • NDL Article ID
    028000540
  • NDL Call No.
    Z53-W539
  • Data Source
    NDL  J-STAGE 
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