The purpose of the proposed research is to characterize recombination between dispersed repeated sequences in eukaryotic organisms. Nonreciprocal recombination events (gene conversions) between repeated sequences are thought to be important in the concerted evolution of multigene families and in the generation of the high degree of genetic polymorphism characteristic of some genetic loci. Reciprocal exchange events between dispersed repeats may also be evolutionarily important since they generate genome rearrangements. In addition to the evolutionary significance, a study of recombination between repeated sequences may also have medical relevance since some congenital abnormalities and the development of certain neoplasms have been associated with chromosomal rearrangements. The yeast Saccharomyces cerevisiae will be the experimental organism used in the proposed study and a genetic system will be developed to examine recombination between duplicated mutant genes at defined positions on nonhomologous chromosomes. Meiotic and mitotic interactions between the mutant genes will be detected by selecting for wild type recombinants. An advantage of the proposed system over previosly used, similar systems will be afforded by fusing one of the mutant genes to an inducible promoter so that reciprocal and nonreciprocal interactions can be distinguished by a simple genetic screen. The system described above will be used for two types of experiments. First, the size of one of the duplicated genes will be systematically varied in order to define the relationship between the size of available sequence homology and the frequency and resolution of interactions between repeated sequences. Second, the system will be used for a mutational analysis of recombination between repeated sequences. Mutations will be isolated which specifically affect the frequency and/or resolution of interactions between the repeated sequences. Mutations isolated in this manner may permit the detection of rec mutations not previously characterized in yeast. In addition, mutations known to affect allelic recimbination will be tested for a similar effect on recombination between repeated sequences on nonhomologous chromosomes. This will establish whether recombination between repeated sequences is mechanistically similar to allelic recombination.
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