The long-term goal of this project is to determine the mechanism of chromosome pairing and segregation during meiosis. The proposed experiments deal with X-Y pairing in Drosophila males. Previous work has identified a short (240bp), highly repeated DNA sequence in the intergenic spacer of the ribosomal DNA which functions as a strong and highly specific pairing site for X-Y disjunction. In the proposed experiments, this sequence will be used as a probe to address fundamental mechanistic questions. Specifically, the sequence will be used to assess: 1) the importance length of homology, chromosomal position and repeat organization in pairing efficacy; 2) the roles of an RNA polymerase I promoter, a topoisomerase I cleavage site, and other sites within the sequence in pairing function; 3) the ability of a pairing site to activate adjacent, non-autonomous sequences to participate in pairing; 4) the presence of heteroduplex DNA (a marker of DNA-level pairing) in meiotic nuclei; and 5) the occurrence of gene conversion within paired sequences. Additional experiments will address the importance of DNA strand transfer and topoisomerase I activities in meiotic pairing in Drosophila. The major issue addressed by these experiments is how homology is communicated in meiotic prophase, in particular, whether it involves DNA-DNA or protein-protein interactions. In addition to providing basic information on the mechanism of chromosome pairing, these experiments are relevant to the mechanisms of nondisjunction and of sterility associated with pairing failure, which are major causes of birth defects and sterility in human populations.
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