Designer nucleases. (a) An engineered zinc finger nuclease (ZFN) in complex with its target DNA (bottom). Surface residues that contact DNA are shown as sticks. Each zinc finger domain contacts 3 or 4 bp in the major groove of the DNA. The complexed Zn²⁺ ion is shown as a purple ball. The cartoon (top) shows a ZFN dimer bound to DNA. ZFN target sites consist of two zinc finger–binding sites separated by a 5 to 7 bp spacer sequence that is cleaved by the FokI nuclease domain. The half sites recognized by a ZFN need not be identical. (b) A TALE protein bound to its target DNA (bottom). TALEN target sites consist of two TALE-binding sites separated by a spacer sequence of 12 to 20 bp (top).