Copper enhances the DNA damage produced by several antitumor drugs, ionizing radiation, and microwaves. The binding of copper to DNA has been proposed as the event determining the specificity observed for copper mediated DNA damage. This work presents data generated by one and two dimensional NMR and by computer assisted modeling of the threedimensional interactions between copper and DNA. Our findings indicate that a) N7 of the guanosine residues (G) are the specific targets for the interaction of copper with double stranded DNA, b) contiguous Gs are more reactive than isolated Gs, and c) the CuDNA binding is fast and reversible. The data and rationale presented in this work may be useful in understanding the molecular action of various anticancer drugs that require copper as a cofactor, hence fostering the design of safe and effective therapeutic agents.