situation, the cloned gene is returned to its homologous location in the genome and becomes inserted at the target locus. This process is a controlled means for the repair of DNA damage and ensures accurate chromosome disjunction during meiosis. The paradigm for thinking about the mechanism of this p- cess has emerged primarily from two sources: (1) The principles of reaction mechanics have come from detailed biochemical analyses of the RecA protein purified from Escherichia coli; and (2) the principles of information transfer have been derived from genetic studies carried out in bacteriophage and fungi. A compelling picture of the process of homologous pairing and DNA strand exchange has been influential in directing investigators interested in gene t- geting experiments. The ability to find and pair homologous DNA molecules enables ac- rate gene targeting and is the central phenomenon underlying genetic recombi- tion. Biochemically, the overall process can be thought of as a series of steps in a reaction pathway whereby DNA molecules are brought into homologous register, the four-stranded Holliday structure intermediate is formed, hete- duplex DNA is extended, and DNA strands are exchanged. Not much is known about the biochemical pathway leading to homologous recombination in euka- otes.

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