Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase

Human exposure to heavy metals is of increasing concern due to their well-documented toxicological and carcinogenic effects and rising environmental levels through industrial processes and pollution. It has been widely reported that such metals can be genotoxic by several modes of action including g...

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Bibliographic Details
Published in:DNA repair 2010-01, Vol.9 (1), p.83-89
Main Authors: Whiteside, James R., Box, Clare L., McMillan, Trevor J., Allinson, Sarah L.
Format: Article
Language:English
Subjects:
Bacteriology
Biological and medical sciences
Cadmium
Cadmium - pharmacology
Copper
Copper - pharmacology
DNA Repair - drug effects
DNA, Single-Stranded - metabolism
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Growth, nutrition, cell differenciation
Heavy metals
Microbiology
Molecular and cellular biology
Molecular genetics
Mutagenesis. Repair
Polynucleotide 5'-Hydroxyl-Kinase - antagonists & inhibitors
Polynucleotide 5'-Hydroxyl-Kinase - metabolism
Polynucleotide kinase
Single strand breaks
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Summary:Human exposure to heavy metals is of increasing concern due to their well-documented toxicological and carcinogenic effects and rising environmental levels through industrial processes and pollution. It has been widely reported that such metals can be genotoxic by several modes of action including generation of reactive oxygen species and inhibition of DNA repair. However, although it has been observed that certain heavy metals can inhibit single strand break (SSB) rejoining, the effects of these metals on SSB end-processing enzymes has not previously been investigated. Accordingly, we have investigated the potential inhibition of polynucleotide kinase (PNK)-dependent single strand break repair by six metals: cadmium, cobalt, copper, nickel, lead and zinc. It was found that micromolar concentrations of cadmium and copper are able to inhibit the phosphatase and kinase activities of PNK in both human cell extracts and purified recombinant protein, while the other metals had no effect at the concentrations tested. The inhibition of PNK by environmentally and physiologically relevant concentrations of cadmium and copper suggests a novel means by which these toxic heavy metals may exert their carcinogenic and neurotoxic effects.
ISSN:1568-7864
1568-7856
DOI:10.1016/j.dnarep.2009.11.004