This proposal explores the organization of DNA in a chromosome, and aims to gain general information about the functional roles of chromosome structure. The power of bacterial genetics, the ability to isolate the chromosome from bacteria, and the many similarities between prokaryotic and eukaryotic chromosome structures motivate the choice of bacteria as a model system. A genetic screen that yields mutants affecting the isolated bacterial chromosome will be explored in depth. Mutations that affect bacterial chromosome structure will guide the biochemical identification of macromolecules that shape chromosome structure. Pseudo revertants of these mutations will suggest physical interactions between macromolecules in the chromosome. The variety of mutations that affect chromosome structure will guide the modelling of the bacterial chromosome toward a very complex structure composed of many different macromolecules, or toward a large but repeating unit structure. These goals are important to the general understanding of an important feature of both prokaryotic and eukaryotic cells. In addition, chromosome rearrangements are associated with a number of birth defects and cancers. Our understanding of chromosome structure and function will guide the treatment and prevention of diseases caused by chromosome rearrangements.
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