The long-term goal of these studies is the elucidation of the molecular mechanisms which underlie chromosome behavior and transmission. Specifically, the experiments are focused on two aspects of chromosome biology in the fruit fly Drosophila melanogaster, namely rDNA magnification and meiotic chromosome segregation. In each case the approach is based on : 1) the isolation of mutations and relevant chromosomal aberrations necessary for genetic dissection; 2) genetic and, where possible, molecular analysis of chromosome behavior; 3) the physical isolation of genes defined by these mutations; and 4) molecular analysis of the structure and expression of these genes. The term rDNA magnification denotes at least two phenomena which result in heritable and stable increases in X chromosomal rDNA redundancy within the germline of rDNA deficient males. We propsoe a series of genetic and molecular experiments aimed at: 1) elucidating the molecular mechanisms of magnification events; 2) identifying the genes or gene systems which carry out these events; and 3) determining the mechanisms by which the cell senses an rDNA deficiency and induces or allows the magnification response. These studies will provide valuable information regarding the mechanism by which cells can stably maintain or alter the redundancy of tandemly repeated genes and some insight into the mechanisms by which the rDNA is expressed and regulated. The second series of experiments centers on a genetic and molecular analysis of the distributive pairing system. This system ensures the regular segregation of nonexchange chromosomes during meiosis I in Drosophila females. Although a few mutants specifically defective in the process have been previously isolated, a much more extensive screen for mutations affecting distributive pairing is proposed. While the purpose of this mutant hunt is to obtain additional alleles of existing loci, it is also hoped that new loci will be identified. Experiments are also proposed to clone at least three genes specifically involved in distributive pairing. The immediate objective of these studies is a molecular analysis of a family of genes which function specifically during meiosis to facilitate chromosome segregation. Over a longer term these experiments will provide the necessary tools to identify the proteins encoded by these genes and determine their cellular and/or chromosomal location. This information will be essential for a molecular understanding of chromosome segregation.
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