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Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase.

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Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase. / Whiteside, James R.; Box, Clare L.; McMillan, Trevor J. et al.
In: DNA Repair, Vol. 9, No. 1, 01.2010, p. 83-89.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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Whiteside JR, Box CL, McMillan TJ, Allinson SL. Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase. DNA Repair. 2010 Jan;9(1):83-89. doi: 10.1016/j.dnarep.2009.11.004

Author

Whiteside, James R. ; Box, Clare L. ; McMillan, Trevor J. et al. / Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase. In: DNA Repair. 2010 ; Vol. 9, No. 1. pp. 83-89.

Bibtex

@article{519991067cda46abbd0dd3b82cafe357,
title = "Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase.",
abstract = "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.",
keywords = "Heavy metals, Polynucleotide kinase, Single strand breaks, Cadmium, Copper",
author = "Whiteside, {James R.} and Box, {Clare L.} and McMillan, {Trevor J.} and Allinson, {Sarah L.}",
year = "2010",
month = jan,
doi = "10.1016/j.dnarep.2009.11.004",
language = "English",
volume = "9",
pages = "83--89",
journal = "DNA Repair",
issn = "1568-7864",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Cadmium and copper inhibit both DNA repair activities of polynucleotide kinase.

AU - Whiteside, James R.

AU - Box, Clare L.

AU - McMillan, Trevor J.

AU - Allinson, Sarah L.

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

KW - Heavy metals

KW - Polynucleotide kinase

KW - Single strand breaks

KW - Cadmium

KW - Copper

UR - http://www.scopus.com/inward/record.url?scp=72949103910&partnerID=8YFLogxK

U2 - 10.1016/j.dnarep.2009.11.004

DO - 10.1016/j.dnarep.2009.11.004

M3 - Journal article

VL - 9

SP - 83

EP - 89

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

IS - 1

ER -