Answer411

From 2006.igem.org

When core sequences are mismatched on the HIN-H107Y mutant, ligation is prevented but synapsis and cleavage is allowed. After recombination, the sites with different core sequences create DNA knots due to "inability to base-pair at crossover site after single exchange of DNA. A second exchange that restores the parental sequence of the recombination sties, but ties a knot in the plasmid DNA, is required for ligation." This would be a possible way to allow for a series of flipping sites to be side by side and keep them from interacting with each other. This question is still unanswered, but interesting info found along the way.

http://www.bio.davidson.edu/courses/synthetic/papers/Sanders_04.pdf