The taming of the shrew

Transposons are mobile genetic elements that can be harmful for the host when mobilized. However, they are also genomic reservoirs for novel genes that can be evolutionarily beneficial. There are many examples of domesticated transposases, which play important roles in the hosts. In most cases domesticated transposases have lost their endonuclease activities and the hosts utilize their DNA-binding properties. However, some other domesticated transposases perform endonuclease activities for host biological processes. Because such a catalytically active transposase is potentially harmful for the integrity of the host genome, its activity should be tightly regulated. The catalytically active domesticated piggyBac transposase Tpb2p catalyzes programmed DNA elimination in the ciliate Tetrahymena. Here, we discuss the regulatory mechanism that prevents unintended DNA cleavage by Tpb2p and compare it to another well-studied catalytically active domesticated transposase, the RAG recombinase in V(D)J recombination. The regulatory mechanisms involve the temporarily regulated expression of the transposases, the target sequence preference of the endonuclease, and the recruitment of the transposases to locally restricted chromatin environments.