Carcinogenesis, Vol 19, 617-621, Copyright © 1998 by Oxford University Press
M Hartmann and A Hartwig
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.
ARTICLES
Disturbance of DNA damage recognition after UV-irradiation by nickel(II) and cadmium(II) in mammalian cells
Department of Biology and Chemistry, University of Bremen, Germany.
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