Whiteside, James R. and Box, Clare L. and McMillan, Trevor J. and Allinson, Sarah L. (2010) Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase. DNA Repair, 9 (1). pp. 83-89. ISSN 1568-7864Full text not available from this repository.
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.
|Journal or Publication Title:||DNA Repair|
|Uncontrolled Keywords:||Heavy metals ; Polynucleotide kinase ; Single strand breaks ; Cadmium ; Copper|
|Subjects:||R Medicine > RL Dermatology|
|Departments:||Faculty of Science and Technology > Lancaster Environment Centre|
Faculty of Health and Medicine > Biomedical & Life Sciences
|Deposited By:||Professor Trevor McMillan|
|Deposited On:||28 Apr 2011 09:07|
|Last Modified:||26 Jul 2012 18:04|
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