Inhibition of Mn2+-induced error-prone DNA synthesis with Cd2+ and Zn2+
| Autor: | Nickolay K. Isaev, A. V. Lakhin, Vyacheslav Z. Tarantul, Elena V. Stelmashook, L. V. Gening |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
DNA Replication
Uveal Neoplasms DNA Repair DNA polymerase DNA-Directed DNA Polymerase Biochemistry Cofactor Bivalent (genetics) Mice Structure-Activity Relationship RNA polymerase I Animals Humans Structure–activity relationship Nucleotide Rats Wistar Melanoma Cells Cultured Nucleic Acid Synthesis Inhibitors chemistry.chemical_classification Manganese Cell Death Dose-Response Relationship Drug biology DNA synthesis Brain DNA General Medicine Molecular biology Rats Zinc Liver chemistry DNA Polymerase iota Biocatalysis biology.protein DNA Polymerase Iota Cadmium |
| Zdroj: | Biochemistry (Moscow). 78:1137-1145 |
| ISSN: | 1608-3040 0006-2979 |
| DOI: | 10.1134/s0006297913100088 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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