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

Kato, Yuichi; Moriwaki, Toshikazu; Funakoshi, Masafumi; Zhang-Akiyama, Qiu-Mei

doi:10.1016/j.mrfmmm.2015.01.001

Cited by 16 publications

(30 citation statements)

References 38 publications

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“…The glp-1 mutant, in which the formation of gonads is prevented, also lives longer (Berman and Kenyon, 2006). We previously reported that deletion of the exo-3 gene causes abnormality in reproduction, including decreased self-brood size (Kato et al, 2015). In this study, we found that the exo-3 mutant has a short lifespan dependent on production of oocytes and gonads.…”

Section: Discussionmentioning

confidence: 47%

“…FUdR extends the lifespan of the exo-3 mutant in a sperm-and gonad-dependent manner Worms homozygous for mutations in exo-3 show abnormalities in reproduction (Kato et al, 2015), and we assumed that FUdR extended the lifespan of exo-3 mutant worms by interfering with fertility. To examine this hypothesis, we measured the lifespan of multiple germline mutants.…”

Section: Resultsmentioning

confidence: 99%

“…TM4374 [exo-3 (tm4374) I] (Kato et al, 2015) was kindly provided by Shohei Mitani (Tokyo Women's Medical College) of the National Bioresource Project for the Nematode. N2 and exo-3 mutant worms were grown and maintained at 20 °C, while fem-1, glp-1 and fem-3 mutant worms were grown and maintained at 16 °C.…”

Section: Methodsmentioning

confidence: 99%

“…As it was assumed that the worms were damaged by picking, we conducted all measurements at 25 °C to finish the experiments in a short period. Worms that did not respond to touch were counted as dead (Kato et al, 2015). Mean lifespans were calculated from the results of three independent experiments, and are presented as means ± SD in figures.…”

Section: Methodsmentioning

confidence: 99%

“…To date, FUdR has not been shown to induce DNA damage in C. elegans. We previously reported that deletion of the exo-3 gene, but not the apn-1 gene, results in decreased lifespan in the absence of FUdR in a ung-1-dependent manner (Kato et al, 2015). EXO-3 and APN-1 are AP endonucleases (Shatilla et al, 2005;Schlotterer et al, 2010;Zakaria et al, 2010;Yang et al, 2012), and UNG-1 is a uracil DNA glycosylase in C. elegans (Nakamura et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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

2016

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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.

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Section: Discussionmentioning

confidence: 47%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

2016

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Genome Stability and Ageing

Gurkar

Gill

Niedernhofer

2016

Healthy Ageing and Longevity

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Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine

Honnen

2017

Arch Toxicol

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In view of increased life expectancy the risk for disturbed integrity of genetic information increases. This inevitably holds the implication for higher incidence of age-related diseases leading to considerable cost increase in health care systems. To develop preventive strategies it is crucial to evaluate external and internal noxae as possible threats to our DNA. Especially the interplay of DNA damage response (DDR) and DNA repair (DR) mechanisms needs further deciphering. Moreover, there is a distinct need for alternative in vivo test systems for basic research and also risk assessment in toxicology. Especially the evaluation of combinational toxicity of environmentally present genotoxins and adverse effects of clinically used DNA damaging anticancer drugs is a major challenge for modern toxicology. This review focuses on the applicability of Caenorhabditis elegans as a model organism to unravel and tackle scientific questions related to the biological consequences of genotoxin exposure and highlights methods for studying DDR and DR. In this regard large-scale in vivo screens of mixtures of chemicals and extensive parallel sequencing are highlighted as unique advantages of C. elegans. In addition, concise information regarding evolutionary conserved molecular mechanisms of the DDR and DR as well as currently available data obtained from the use of prototypical genotoxins and preferential read-outs of genotoxin testing are discussed. The use of established protocols, which are already available in the community, is encouraged to facilitate and further improve the implementation of C. elegans as a powerful genetic model system in genetic toxicology and biomedicine.

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

Cited by 16 publications

References 38 publications

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

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

Genome Stability and Ageing

Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine

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