The purpose of this project is the collaborative study of the physical properties of a wide variety of biological macromolecules with the goal of correlating these properties with the structure and function of the macromolecules. Analytical ultracentrifugation and mathematical modeling are the principal research techniques used. An area of major emphasis has been collaborative studies with the laboratory of Dr. Samuel Wilson (NIEHS) on proteins involved in DNA transcription initiation and in DNA repair. New studies in progress are (1) the interactions between DNA Ligase I and the replication protein, proliferating cell nuclear antigen (PCNA); (2) the interaction mechanisms between the XRCC1(1-183) protein and DNA polymerase-beta and its subdomains; (3) the study of DNA transcription initiation repression by gal repressor (galR) and the HU protein; (4) the interactions between AP endonuclease and DNA, DNA polymerase-beta and DNA, and both together with DNA. Collaborative studies with the laboratory of Dr. Thomas Kunkel (NIEHS) on the interactions involving MutL homologs has been initiated. Research on the cell cycle regulatory protein p53 with the laboratory of Dr. Ettore Appella (NCI) have been continued with investigations of the thermodynamics of the interactions of the tetramerization domain of p53 and the effect of truncations of that domain on that association. Studies on the self association of translin, a protein involved in translocation of chromosomal DNA have been done in a collaboration with Dr. Myun Ki Han (Georgetown University). Translin has been found to undergo a reversible monomer-octamer association and the octameric form binds damaged single stranded DNA. Measurements of the density and viscosity of aqueous and deuterium oxide buffers have been continued. These values, not previously available, are essential for zonal sedimentation velocity experiments of critical importance in a variety of studies being conducted by the Resource.
