A single d(GpG) cisplatin adduct on the estrogen response element decreases the binding of the estrogen receptor.
Both cisplatin and the estrogen receptor (ER) are known to bend DNA. The influence of the bending of sequences by the d(GpG)cisPt adduct binding of ER to estrogen response element (ERE)-like sequences was examined. Three ERE-like oligonucleotides with different affinities for ER and which include a GG in the linker sequence were designed in order to form a single central d(GpG)cisPt adduct. Using electrophoretic mobility shift assay and Scatchard analysis, it was shown that the presence of a single d(GpG)cisPt adduct in the linker sequence decreases the ER affinity for DNA. These results do not support a critical role of a DNA bend in the initial recognition of ERE by ER. Then, the platination of DNA outside of the ERE half-sites decreases the interaction of ER with ERE.
Massaad-Massade
L
L
Université René Descartes, Laboratoire de Toxicologie Moléculaire, U-490 INSERM, 45 rue des Saints-Pères, 75270, Paris, France. liliane.massade@biomedicale.univ-paris5.fr
Massaad
C
C
Legendre
F
F
Bas
V
V
Chottard
J
J
Beaune
P
P
Barouki
R
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009690:Nucleic Acid Conformation; D011960:Receptors, Estrogen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D018736:DNA Adducts; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; C057270:cisplatin-DNA adduct; D004247:DNA; D002945:Cisplatin