A tetramer of the Flp recombinase silences the trimers within it during resolution of a Holliday junction substrate.

Recombination catalyzed by the Flp site-specific recombinase involves breakage and joining of four DNA strands between two target substrates. The reaction is carried out in two steps of pairwise strand exchanges by a DNA-protein assembly in which four Flp monomers act cooperatively to execute strand cleavage and joining. Two models for recombination have been proposed. In the trimer model, the two active sites required for each step are assembled from three Flp monomers. In the tetramer (or dimer of asymmetric dimers) model, the two active sites are assembled from four Flp monomers, two monomers each contributing one active site. Experiments in which the two models challenge each other reveal that, within the Flp tetramer arranged on a Holliday junction, the two active sites required for its resolution are derived from all four, rather than three, Flp monomers. Thus, the relative protein subunit configuration of the tetramer silences the trimers within it by excluding them from assembling a functional active site pair.