Inhibition of Mn <sup>2+</sup>-Induced Error-Prone DNA Synthesis with Cd <sup>2+</sup> and Zn <sup>2+</sup>
Divalent metal cations are key components in the reaction of DNA synthesis. They are involved in the catalytic mechanism of all DNA polymerases as cofactors. It is also known that Mn 2+ can considerably decrease the fidelity of DNA synthesis. The results obtained in this work show that Cd 2+ and Zn 2+ selectively inhibit Mn 2+-induced error-prone DNA synthesizing activity in extracts of cells from human and mouse tissues. Low concentrations of these cations can also efficiently inhibit the activity of homogeneous preparations of DNA polymerase iota (Pol ι), which is known to play a major role in Mn 2+-induced error-prone DNA synthesizing activity in cell extracts. Using a primary culture of cerebellum granule cells of postnatal rats, we showed that low concentrations of Cd 2+ significantly increased the survival of cells in the presence of toxic doses of Mn 2+. Thus, we demonstrated that low concentrations of Cd 2+ in some cases can positively affect cells, although it is widely acknowledged that this metal is not a necessary microelement and is toxic for the organism.