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

Merle M. Nicolai, Ann Kathrin Weishaupt, Jessica Baesler, Vanessa Brinkmann, Anna Wellenberg, Nicola Winkelbeiner, Anna Gremme, Michael Aschner, Gerhard Fritz, Tanja Schwerdtle, Julia Bornhorst

Research output: Contribution to journalArticlepeer-review

Abstract

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 Mninduced 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.

Original languageEnglish (US)
Article number10905
JournalInternational Journal of Molecular Sciences
Volume22
Issue number20
DOIs
StatePublished - Oct 1 2021

Keywords

  • Caenorhabditis elegans
  • DNA damage response
  • DNA repair
  • Manganese
  • Oxidative stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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