PHYSICAL AND BIOLOGICAL APPROACHES TO Z-DNA

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Z-DNA, the left handed double helix, has been seen in crystals and solutions of synthetic polydeoxynucleotides. Evidence exists that suggests that Z-DNA is also found in vivo. If so, Z-DNA may be a regulator of gene expression or, because of the chemical reactivity of its constituent bases, an important site of carcinogen action. The purpose of the proposed research is to better understand the phenomenon of Z-DNA on both a physical and biological level, and ultimately to understand the relationship of DNA structure to its biological function. To determine the structural parameters stabilizing the Z form of DNA, defined sequence polydeoxynucleotides will be synthesized by a combination of chemical and biochemical methods, and their ability to assume the Z form will be correlated with their chemical structures. This is intended to develop the ability to predict under what circumstances any particular sequence will be in the Z form. Additionally, using topological properties inherent in the left handed helix when cloned in closed circular plasmids, a search will be conducted for sequences of genomic DNA that can exist in the Z form and also for proteins that bind specifically to Z-DNA. This is intended to show the existence of Z-DNA in vivo, or to rule it out as a general biological phenomenon. The methods that will be in place for the above projects will also be used to look at unanswered questions concerning the B-A transition in DNA and to examine the structure of DNA sequences found in eukaryotes that have nucleoprotein structures different from bulk chromatin.