Sin is a serine resolvase from S. aureus that catalyzes site-specific DNA rearrangements in a topologically regulated manner. Regulation is mediated by a conformational switch: the WT protein remains in an inactive conformation unless it is incorporated into a large complex termed the synaptosome. This complex traps 3 negative nodes in the DNA and includes a DNA bending protein and additional copies of the recombinase. Regulation can be circumvented, however, by certain mutations that favor the active form of the protein in the absence of cofactors.

Using a combination of structural, biochemical, and genetic tools, we have constructed a model for the full synaptosome. We have also shown that catalytic activation correlates directly with tetramerization of the recombinase, which otherwise exists in solution as dimers and/or monomers. Finally, we are beginning to address how well our model applies to related serine recombinases such as the resolvase from Tn3.