DNA-BINDING AND PHOTOCLEAVAGE BY URANYL(VI) (UO2(2+)) SALTS

Artikel i vetenskaplig tidskrift, 1992

The interaction of the uranyl(VI) ion (UO22+) with DNA and its light-induced cleavage of DNA has been studied using flow-linear dichroism and P-32-endlabeled oligonucleotides. It was found that binding of uranyl ion to DNA is a prerequisite for photocleavage; from run-off experiments the binding constant was estimated to be of the order of 10(10) M-1 at pH 4. The angular orientation of the [O=U=O]2+ chromophore is consistent with binding by bridging phosphate groups on opposite strands of the minor groove of DNA; at higher DNA concentration aggregation indicates intermolecular bridging as well. The uranyl-mediated photocleavage of DNA is not influenced by the presence of O2, is more efficient at low pH (<7), and is virtually absent at pH 8.5. Subsequent treatment of uranyl photocleaved DNA with hot piperidine does not significantly increase the cleavage. The free nucleobases (adenine, cytosine, guanine, and thymine) were the major ethanol-soluble products to be observed after uranyl photocleavage of calf thymus DNA. From experiments using P-32-endlabeled and methyl-phosphonate-containing oligonucleotides, it was concluded that upon irradiation attack by the uranyl ion occurs next to the phosphate to which it is bound, with equal preference for the 3'- and 5'-deoxyribose.