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The present invention relates to a method for enhancing the efficiency of rare-cutting endonucieases such as meganucleases. More specifically, the present invention concerns a method for the creation of fusion proteins that consist of one or more "enhancer" domains fused to at least one rare-cutting endonuclease-derived scaffold in a single polypeptide chain for simple and efficient vectorization. The present invention also relates to engineered chimeric rare-cutting endonucieases, vectors, compositions and kits used to implement the method and use of said chimeric rare-cutting endonucieases according to the invention for various applications ranging from homologous gene targeting to targeted mutagenesis and sequence removal.