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Manganese-induced infidelity of DNA synthesis as a possible cause of manganism

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Abstract

The impact of the eight most common bivalent metal cations (Mg2+, Mn2+, Co2+, Cd2+, Zn2+, Ni2+, Ca2+, and Cu2+) on the operation of the whole complex of DNA polymerases in mice brain cell extracts was tested. A decrease in the fidelity of the DNA synthesis was observed in the presence of several metals; among them, Mn2+ had the most significant effect. It was also demonstrated that this effect was mainly due to DNA polymerase iota (Pol ι) activity. It is well-known that occupational or environmental exposure to excessive Mn can lead to development of neurodegenerative diseases (e.g., manganism). However, the molecular mechanism underlying these pathologies is still unknown. Our results suggest that the neurotoxic effect of Mn2+ may be associated with local activation of highly error-prone Pol ι that increases incorrect DNA synthesis at elevated concentrations of this metal.

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Authors and Affiliations

  1. Institute of Molecular Genetics, Russian Academy of Sciences, pl. Akademika Kurchatova 2, Moscow, 123182, Russia

    A. V. Lakhin, V. Z. Tarantul & L. V. Gening

Authors
  1. A. V. Lakhin
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  2. V. Z. Tarantul
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  3. L. V. Gening
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Correspondence to A. V. Lakhin.

Additional information

Original Russian Text © A.V. Lakhin, V.Z. Tarantul, L.V. Gening, 2014, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2014, No. 1, pp. 15–21.

The article was translated by the authors.

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Lakhin, A.V., Tarantul, V.Z. & Gening, L.V. Manganese-induced infidelity of DNA synthesis as a possible cause of manganism. Mol. Genet. Microbiol. Virol. 29, 16–22 (2014). https://doi.org/10.3103/S0891416814010030

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  • DOI: https://doi.org/10.3103/S0891416814010030

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