The interwoven architecture of the Mu transposase couples DNA synapsis to catalysis

Mu transposition occurs exclusively using a pair of recombination sites found at the ends of the phage genome. To address the mechanistic basis of this specificity, we have determined both where the individual subunits of the tetrameric transposase bind on the DNA and where they catalyze DNA joining. We demonstrate that subunits do not catalyze recombination at the site adjacent to where they are bound, but rather on the opposite end of the phage genome. Furthermore, subunits bound to two different sites contribute to catalysis of one reaction step. This interwoven subunit arrangement suggests a molecular explanation for the precision with which recombination occurs using a pair of DNA signals and provides an example of the way in which the architecture of a protein-DNA complex can define the reaction products.