Merle Marie Nicolai, Ann-Kathrin Weishaupt, Jessica Baesler, Vanessa Brinkmann, Anna Wellenberg, Nicola Lisa Winkelbeiner, Anna Gremme, Michael Aschner, Gerhard Fritz, Tanja Schwerdtle, Julia Bornhorst
- Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this studyAlthough manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.…
MetadatenAuthor details: | Merle Marie NicolaiORCiD, Ann-Kathrin WeishauptORCiD, Jessica BaeslerORCiDGND, Vanessa BrinkmannORCiDGND, Anna Wellenberg, Nicola Lisa WinkelbeinerORCiDGND, Anna Gremme, Michael AschnerORCiDGND, Gerhard Fritz, Tanja SchwerdtleORCiDGND, Julia BornhorstORCiDGND |
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URN: | urn:nbn:de:kobv:517-opus4-523275 |
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DOI: | https://doi.org/10.25932/publishup-52327 |
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ISSN: | 1866-8372 |
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Title of parent work (German): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
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Publication series (Volume number): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1173) |
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Publication type: | Postprint |
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Language: | English |
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Date of first publication: | 2021/09/05 |
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Publication year: | 2021 |
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Publishing institution: | Universität Potsdam |
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Release date: | 2021/10/20 |
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Tag: | Caenorhabditis elegans; DNA damage response; DNA repair; manganese; oxidative stress |
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Issue: | 1173 |
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Number of pages: | 18 |
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Source: | Int. J. Mol. Sci. 2021, 22(20), 10905; https://doi.org/10.3390/ijms222010905 |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
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DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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Peer review: | Referiert |
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Publishing method: | Open Access / Green Open-Access |
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License (German): | CC-BY - Namensnennung 4.0 International |
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External remark: | Bibliographieeintrag der Originalveröffentlichung/Quelle |
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