ZFNs operate by first binding to their target DNA sequence through the zinc finger domains. Each zinc finger can recognize a specific triplet of DNA bases, allowing for modular assembly of zinc finger arrays to target longer sequences. Once bound, the FokI nuclease domains dimerize, creating a double-strand break. This break can then be repaired by the cell's natural DNA repair mechanisms, such as non-homologous end joining (NHEJ) or homology-directed repair (HDR), leading to targeted genetic modifications.
