POLYAMINE-POLYNUCLEOTIDE INTERACTIONS

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The overall goal is to understand the mechanisms whereby DNA collapses and forms ordered aggregates in response to changes in ionic conditions. The aim throughout is to understand the relative importance of electrostatics, site binding, water structure modulation, and stabilization of novel DNA helix geometries as ways in which ions exert their influence. Specific aims are to 1. Develop a consistent statistical thermodynamic and kinetic mechanism that explains the striking constancy os size of toroidal and rodlike DNA particles collapsed by polyamines and hexammine cobalt(III), independent of the DNA molecular weight, as measured by laser light scattering and electron microscopy. 2. Perform computer simulations on models of water near charged or polar surfaces that will test the plausibility of the idea that ions act not only electrostatically or by binding to specific sites, but also by their effects on water structure near DNA surfaces. 3. Use chemical, antibody, and spectroscopic probes and helix- coil transition theory to test the idea that condensation of natural DNA may be the result of the formation and subsequent association of regions of non-B DNA (e.g. Z or P form) in randomly occurring sequences of alternating purine-pyrimidine residues. 4. Develop a polymer statistical thermodynamic theory of DNA collapse by anionic polypeptides that takes both polymer-polymer incompatibility and ionic polymer expansion into account, and perform light scattering and sedimentation experiments that will map out a phase diagram to compare with theoretical expectations. Compaction of DNA by simple ions and ionic polymers is of interest as a model for DNA packaging in virus particles and chromatin, and may lead to better understanding of the physical mechanisms underlying regulation of gene expression and DNA replication.