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DNA-binding domains including the basic helix-loop-helix, zinc finger, helix-turn-helix and leucine zipper motifs have been used in construction of sequence-specific nucleases. Of these, zinc fingers have been suggested the most important due to their modularity, allowing construction of a tailor-made DNA-binding domain.
The nuclease domain is responsible for physical cleavage of DNA strands and may introduce either single stranded or double-stranded breaks. FokI is an example of a sequence-specific endonuclease whose non-specific nuclease domain introduces double stranded breaks and has been used in a variety of experiments including identification of high- and low-affinity binding sites of transcription factors in vitro, to study recruitment of factors to promoter sites in vivo using protein position identification with a nuclease tail assay and to study proteins specific to interaction with DNA in the Z-DNA conformation (Durai et al., 2005 and references therein).