Metal ions are essential in the function of nuclease enzymes. Typically, Mg2+ ions are found in nucleases, however Mn2+ can also be found (but due to the lower physiological concentration of manganese, it is less frequently seen).
In nucleases with one metal ion, the metal ion stabilises the complex, supporting substrate-assisted cleavage. This requires the right balance to prevent too much stabilisation, which would prevent the cleaved DNA from leaving the enzyme.
Where two metal ions are present in a nuclease, one supports the formation and positioning of the nucleophile, while the second interacts with the leaving oxyanion. The metal ions also contribute to the stability of the pentavalent phosphate intermediate, before the scissile bond is broken.
Three metal ions can be found, with two having similar roles to the two metal ion nucleases. The function of the third metal ion is not fully understood, however it is thought to have a stabilising role instead of being catalytic.