Inhibition of Mn(2+)-induced error-prone DNA synthesis with Cd(2+) and Zn(2+).
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.
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. geni@img.ras.ru.
L V
LV
Gening
A V
AV
Lakhin
E V
EV
Stelmashook
N K
NK
Isaev
V Z
VZ
Tarantul
D000818:Animals; D055162:Biocatalysis / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008099:Liver / Q000201:enzymology; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014604:Uveal Neoplasms / Q000201:enzymology; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*; D000094769:DNA Polymerase iota
D019384:Nucleic Acid Synthesis Inhibitors; D002104:Cadmium; D008345:Manganese; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D015032:Zinc; D000094769:DNA Polymerase iota