The role of metal ions in DNA polymerase catalysis. (a) The DNA polymerase active site contains two divalent metal ions (Mg2+) held in place by residues in the palm, including conserved Asp residues. The two ions play an essential role in catalysis, as described in the text. (b) The 3′→5′ exonuclease also uses a two-metal-ion-catalyzed reaction.