Polyamines are small charged molecules found in all living cells and required for cell growth and proliferation. The specific functions carried out by polyamines in the cell are poorly understood, but their properties strongly suggest that they interact with nucleic acids. This proposal is to carry out a systematic study of the interaction between polyamines and chromosome components, including DNA, nucleosome core particles, nucleosomes, oligonucleosomes, and "long" chromatin. It is known that the interaction between polyamines and nucleosomes or nucleosome core particles is considerably more complicated than a purely electrostatic interaction and that polyamines can cause a conformational change in nucleosome core particles. Future studies will extend the work with thermal denaturation and circular dichroism, to larger chromatin components, and will introduce two new methods for studying the interaction at all levels, namely "footprinting" with hydroxyl radicals, and photoaffinity labeling. The study is particularly focused on the effect of polyamine acetylation because preliminary work has confirmed the possibility that this process may be important in the dymanics of changing chromatin structure, possibly coordinated with histone acetylation. The use of photoaffinity labeling to probe the distribution of polyamines in vivo will also be investigated. While the function of polyamines in the cell is currently unknown, their ubiquitous distribution suggests some fundamental role in maintaining gene structure or function. The results of this study on polyamine interactions should aid materially in developing a testable model for their role in cell metabolism.
