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Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways
Manganese is an essential trace element; nevertheless, on conditions of overload, it becomes toxic, with neurotoxicity being the main concern. Chromate is a well-known human carcinogen. The underlying mechanisms seem to be oxidative stress as well as direct DNA damage in the case of chromate, but al...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298927/ https://www.ncbi.nlm.nih.gov/pubmed/37373538 http://dx.doi.org/10.3390/ijms241210392 |
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author | Haberland, Vivien M. M. Magin, Simon Iliakis, George Hartwig, Andrea |
author_facet | Haberland, Vivien M. M. Magin, Simon Iliakis, George Hartwig, Andrea |
author_sort | Haberland, Vivien M. M. |
collection | PubMed |
description | Manganese is an essential trace element; nevertheless, on conditions of overload, it becomes toxic, with neurotoxicity being the main concern. Chromate is a well-known human carcinogen. The underlying mechanisms seem to be oxidative stress as well as direct DNA damage in the case of chromate, but also interactions with DNA repair systems in both cases. However, the impact of manganese and chromate on DNA double-strand break (DSB) repair pathways is largely unknown. In the present study, we examined the induction of DSB as well as the effect on specific DNA DSB repair mechanisms, namely homologous recombination (HR), non-homologous end joining (NHEJ), single strand annealing (SSA), and microhomology-mediated end joining (MMEJ). We applied DSB repair pathway-specific reporter cell lines, pulsed field gel electrophoresis as well as gene expression analysis, and investigated the binding of specific DNA repair proteins via immunoflourescence. While manganese did not seem to induce DNA DSB and had no impact on NHEJ and MMEJ, HR and SSA were inhibited. In the case of chromate, the induction of DSB was further supported. Regarding DSB repair, no inhibition was seen in the case of NHEJ and SSA, but HR was diminished and MMEJ was activated in a pronounced manner. The results indicate a specific inhibition of error-free HR by manganese and chromate, with a shift towards error-prone DSB repair mechanisms in both cases. These observations suggest the induction of genomic instability and may explain the microsatellite instability involved in chromate-induced carcinogenicity. |
format | Online Article Text |
id | pubmed-10298927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102989272023-06-28 Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways Haberland, Vivien M. M. Magin, Simon Iliakis, George Hartwig, Andrea Int J Mol Sci Article Manganese is an essential trace element; nevertheless, on conditions of overload, it becomes toxic, with neurotoxicity being the main concern. Chromate is a well-known human carcinogen. The underlying mechanisms seem to be oxidative stress as well as direct DNA damage in the case of chromate, but also interactions with DNA repair systems in both cases. However, the impact of manganese and chromate on DNA double-strand break (DSB) repair pathways is largely unknown. In the present study, we examined the induction of DSB as well as the effect on specific DNA DSB repair mechanisms, namely homologous recombination (HR), non-homologous end joining (NHEJ), single strand annealing (SSA), and microhomology-mediated end joining (MMEJ). We applied DSB repair pathway-specific reporter cell lines, pulsed field gel electrophoresis as well as gene expression analysis, and investigated the binding of specific DNA repair proteins via immunoflourescence. While manganese did not seem to induce DNA DSB and had no impact on NHEJ and MMEJ, HR and SSA were inhibited. In the case of chromate, the induction of DSB was further supported. Regarding DSB repair, no inhibition was seen in the case of NHEJ and SSA, but HR was diminished and MMEJ was activated in a pronounced manner. The results indicate a specific inhibition of error-free HR by manganese and chromate, with a shift towards error-prone DSB repair mechanisms in both cases. These observations suggest the induction of genomic instability and may explain the microsatellite instability involved in chromate-induced carcinogenicity. MDPI 2023-06-20 /pmc/articles/PMC10298927/ /pubmed/37373538 http://dx.doi.org/10.3390/ijms241210392 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Haberland, Vivien M. M. Magin, Simon Iliakis, George Hartwig, Andrea Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title | Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title_full | Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title_fullStr | Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title_full_unstemmed | Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title_short | Impact of Manganese and Chromate on Specific DNA Double-Strand Break Repair Pathways |
title_sort | impact of manganese and chromate on specific dna double-strand break repair pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298927/ https://www.ncbi.nlm.nih.gov/pubmed/37373538 http://dx.doi.org/10.3390/ijms241210392 |
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