Inhibition of Mn²⁺-Induced Error-Prone DNA Synthesis with Cd²⁺ and Zn²⁺

---

L. V. Gening^1*, A. V. Lakhin¹, E. V. Stelmashook², N. K. Isaev^2,3, and V. Z. Tarantul¹

¹Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, 123182 Moscow, Russia; E-mail: geni@img.ras.ru

²Department of Brain Research, Institute of Neurology, Russian Academy of Medical Sciences, Pereulok Obukha 5, 105064 Moscow, Russia

³Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

^* To whom correspondence should be addressed.

Received May 23, 2013; Revision received June 17, 2013

---

Bivalent metal cations are key components in the reaction of DNA synthesis. They are necessary for all DNA polymerases, being involved as cofactors in catalytic mechanisms of nucleotide polymerization. It is also known that in the presence of Mn²⁺ the accuracy of DNA synthesis is considerably decreased. The findings of this work show that Cd²⁺ and Zn²⁺ selectively inhibit the Mn²⁺-induced error-prone DNA polymerase activity in extracts of cells from human and mouse tissues. Moreover, these cations in low concentrations also can efficiently inhibit the activity of homogeneous preparations of DNA polymerase iota (Pol ι), which is mainly responsible for the Mn²⁺-induced error-prone DNA polymerase activity in cell extracts. Using a primary culture of granular cells from postnatal rat cerebellum, we show that low concentrations of Cd²⁺ significantly increase cell survival in the presence of toxic Mn²⁺ doses. Thus, we have shown that in some cases low concentrations of Cd²⁺ can display a positive influence on cells, whereas it is widely acknowledged that this metal is not a necessary microelement and is toxic for organisms.

---

KEY WORDS: DNA polymerase iota, manganese, manganism, cadmium

DOI: 10.1134/S0006297913100088

---