Journal Article

Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells.

M Hartmann and A Hartwig

in Carcinogenesis

Volume 19, issue 4, pages 617-621
Published in print April 1998 | ISSN: 0143-3334
Published online April 1998 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/19.4.617
Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells.

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Nickel(II) and cadmium(II) have been shown previously to inhibit the incision step of nucleotide excision repair. By applying a gel-mobility-shift assay and HeLa nuclear extracts the effect of both metals on the damage recognition step of the repair process was investigated. Two proteins of 34 and 40 kDa were identified that bind with high affinity to a UV-irradiated synthetic oligonucleotide. When applying nuclear extracts from HeLa cells treated with 50 microM nickel(II) and higher, there was a dose-dependent decrease in protein binding; this effect was largely reversible by the addition of magnesium(II) to the binding reaction. In the case of cadmium(II), a dose-dependent inhibition of DNA-protein interactions was detected at 0.5 microM and higher, which was almost completely reversible by the addition of zinc(II). Therefore, compounds of both metals disturb DNA-protein interactions essential for the initiation of nucleotide excision repair most likely by the displacement of essential metal ions.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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