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 Dr. Edith Wolff (NIDR) on the interactions involved in the formation of the hypusine residue in the iIF-5A protein have been continued. Research on the cell cycle regulatory protein p53 with members of Dr. Ettore Appellas laboratory (NCI) have been continued with investigations of the interactions of the carboxyterminal domain of p53 with casein II kinase and with the transcription activation factor protein (TAF) which is a part of the transcription complex. This has required investigation of the reversible self-associative properties of TAF, which has been found to undergo a reversible monomer-tetramer association. Additional studies on the effects of phosphorylation on the interactions of the tetramerization domain of p53 have been carried out. 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 Univ.) Translin has been found to undergo a reversible monomer-octamer association and the octameric form binds damaged single stranded DNA. Extensive new measurements of the density and viscosity of aqueous and deuterium oxide buffers have been made. 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 - DNA repair enzymes, p53, ilF-5A, protein-nucleic acid interactions, analytical ultracentrifugation

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Intramural Research (Z01)
Project #
1Z01OD010184-02
Application #
6290681
Study Section
Special Emphasis Panel (BE)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Office of the Director, National Institutes of Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code