It is well known that the wild type Cu,Zn superoxide dismutase (holo SOD) catalyzes the conversion of superoxide anion to peroxide hydrogen and dioxygen. However, a new function of holo SOD, i.e., nucleolytic activity has been found [W. Jiang, T. Shen, Y. Han, Q. Pan, C. Liu, J. Biol. Inorg. Chem. 11 (2006) 835-848], which is linked to the incorporation of exogenous divalent metals into the enzyme-DNA complex. In this study, the roles of exogenous divalent metals in the nucleolytic activity were explored in detail by a series of biochemical experiments. Based on a non-equivalent multi-site bin...