Fig. (3).

Endonuclease-induced gene targeting approaches. Upon cleavage, DNA repair mechanisms may result in one of several outcomes. When a double-strand break is targeted between two direct repeats (a), homologous recombination can result in the deletion of one repeat together with the intervening sequence. Gene insertion (b) or correction (c) can be achieved by the introduction of a DNA repair matrix containing sequences homologous to the endogenous sequence surrounding the DNA break. Mutations can be corrected either at or distal to the break, with the frequency of correction decreasing with increasing distance. The misrepair of DNA ends by error-prone non-homologous end joining (d) can result in insertions or deletions of various sizes, leading to gene inactivation.