Hydrolytic cleavage and a transesterification reaction involved in transpositions. These are the reactions promoted by integrases and transposases. In both (a) and (b), the left side shows the fate of the DNA, and the right side shows reaction details. (a) The first step in transposition is usually the attack of a water molecule on a phosphodiester bond at each end of the transposon to create free 3′ ends. This creates a nick in one DNA strand at each transposon end, but the other DNA strand remains intact. The additional steps illustrate the reactions that complete the excision of the transposon in cut-and-paste transposition. The transposase catalyzes attack of each liberated 3′ hydroxyl on a phosphodiester bond in the complementary strand, immediately opposite. The transposon is fully excised, with its ends structured as closed hairpin loops, and a double-strand break is left in the DNA where the transposon originated. The closed hairpin loops are opened by yet another hydrolytic cleavage of a phosphodiester bond, again catalyzed by the transposase. (b) The 3′-OH thus liberated acts as a nucleophile, attacking another phosphodiester bond in the target DNA. The attacked bond is cleaved, and a new bond is created.