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4 Homing Endonucleases

John E. Mueller, Mary Bryk, Nick Loizos, Marlene Belfort


Homing endonucleases are a group of enzymes whose catalytic activity results in self-propagation. The sequences that code for these endonucleases usually interrupt genes by localizing as open reading frames in introns or as inframe spacers in protein-coding sequences. The target of a homing endonuclease is its cognate intronless or spacerless allele. The endonuclease initiates a DNA mobility or “homing” event by making a double-strand cut in its target. Repair of the cleaved allele results in the conversion of this gene to the interrupted endonuclease-encoding form. Homing endonucleases are widespread, found in all three kingdoms and in a range of genetic environments, which include mitochondrial, chloroplast, nuclear, and bacteriophage genomes (Table 1). Although the discovery of these endonucleases is recent, genetic consequences attributable to their presence have been observed for some time (see Fig. 1)

We review here the history and general properties of homing endonucleases, point out both similarities and differences among the individual enzymes, and address the evolutionary implications of endonuclease gene mobility.

In 1970, the unidirectional transfer of a Saccharomyces cerevisiae genetic marker, termed omega (ω), from ω+ to ω yeast strains, was reported (Coen et al. 1970), sparking a great deal of interest regarding the role of nonreciprocal recombination in yeast mitochondrial genetics. With the discovery of restriction enzymes and the introduction of advanced molecular techniques, the ω locus was mapped to an intron in the mitochondrial large ribosomal RNA gene (L-rRNA gene) (Dujon and Michel 1976; Bos et al. 1978; Heyting...

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