Chromosomes are DNA molecules that contain the genetic blueprint of an organism. Maintaining the structural integrity of chromosomes is essential for the normal growth and differentiation of all eukaryotic organisms. Aberrations in chromosome structure are a hallmark of many congenital abnormalities and genetic diseases of humans. Many significant questions remain concerning the structure of eukaryotic chromosomes. The long-term objective of this research is to elucidate the large-scale euchromatic-heterochromatic domain structure of eukaryotic chromosomes, and determine how interactions between these domains can alter chromosome structure during development. A small, molecularly-tractable model chromosome, the 1300 kb Dp (1;f) 1187 mini chromosome of Drosophila melanogaster provides a unique opportunity to address previously inaccessible questions about chromosome structure. Initial studies have already demonstrated that restriction fragments of Dp (1;f) 1187 that cross euchromatic-heterochromatic functions and extend into heterochromatic domains have highly unusual properties including being selectively retained in agarose gels during DNA-blotting protocols and undergoing structural changes that alter fragment size. These properties vary between tissues both quantitatively and qualitatively.
The specific aim of this research will be to extend these observations and: 1) determine the structure of Dp (1;f) 1187 in tissues of differing chromosome structure including polyploid, polytene, diploid and haploid chromosomes; 2) determine the generality of the initial observations by characterizing the properties of heterochromatic regions of the normal chromosome complement and 3) determine the molecular basis for the unusual physical properties of Dp (1;f) 1187 heterochromatic DNA. The novel nature of observations already made using this system suggest that continued analysis will reveal unanticipated aspects of DNA and chromosome structure of broad significance.
