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Effects of manganese on genomic integrity in the multicellular model organism Caenorhabditis elegans

  • 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.show moreshow less

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Author 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
DOI:https://doi.org/10.3390/ijms222010905
ISSN:1422-0067
Title of parent work (English):International Journal of Molecular Sciences
Publisher:MDPI
Place of publishing:Basel
Publication type:Article
Language:English
Date of first publication:2021/09/05
Publication year:2021
Release date:2021/10/20
Tag:Caenorhabditis elegans; DNA damage response; DNA repair; manganese; oxidative stress
Volume:22
Issue:20
Article number:10905
Number of pages:16
Funding institution:Universität Potsdam
Funding number:PA 2021_128
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie
DDC classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Peer review:Referiert
Grantor:Publikationsfonds der Universität Potsdam
Publishing method:Open Access / Gold Open-Access
License (German):License LogoCC-BY - Namensnennung 4.0 International
External remark:Zweitveröffentlichung in der Schriftenreihe Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1173
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