Cre-mediated site-specific recombination. (A) Schematic of site-specific recombination proceeding via the BS-S complex. After DNA cleavage by the active recombinases (green) within the BS-S complex, strand exchange forms a BS-HJ. Isomerization occurs between this and the TS-HJ; after another round of cleavage and strand exchange, a TS-P synaptic complex is formed. Positions of the donor and acceptor (green and red, respectively) and interfluorophore distance measurements from crystal structure (PDB: 2HOI) are shown (SI Text). (B) Sequence of loxP site. Cre binding sites in lowercase, and asymmetric central region in uppercase; arrows indicate cleavage positions. TS and BS nomenclature as in Ghosh et al. (6) (C) Crystal structure of Cre in BS synaptic complex with DNA (PDB:2HOI, 21); DNA was extrapolated (gray) to the labeling site, and mean fluorophore positions are shown as colored circles (SI Text).