[The manganese-induced infidelity of the DNA synthesis as a possible cause of manganism]

Abstract

The impact of the 8 most common bivalent metal cations (Mg2+, Mn2+, Co2+, Cd2+, Zn2+, Ni2+, Ca2+, 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+ caused the most significant effect. It was also demonstrated that this effect was mainly due to the DNA polymerase iota (Pol iota) activity. It is well known that occupational or environmental exposure to excessive Mn could 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 iota that increases incorrect DNA synthesis at elevated concentrations of this metal.