The integrity of DNA within cells is challenged continuously by a myriad of chemical, physical, and biological agents in the environment. The biological consequences of these DNA modifications are modulated by the efficiency and fidelity of DNA repair mechanisms. Incomplete and/or error- prone repair may lead to toxic,mutagenic and carcinogenic responses at the cellular and organismal level. In light of the effects of environment agents on human health, The university of Texas Medical Branch has assembled a substantial research faculty who are working toward elucidation of the molecular and cellular mechanisms of DNA damage and repair. Five focused Research Cores have evolved as follows: - Structure-Function Analyses of DNA Repair Enzymes and DNA - Interactive Proteins-Biophysical Studies - DNA Repair Enzymes-Biochemical Mechanisms of Action - Gene Cloning, Control of Gene Expression and Signal Transduction - DNA Mutagenesis - Molecular Epidemiology The Research Cores comprise the intellectual basis for a highly integrated NIEHS Center. To bring these scientific programs to their full potential, we propose to establish state-of-the-art service cores to facilitate collaborative research projects among Center Investigators as well as to enhance the scope and quality of individual Center Investigators. The proposed Center will make it possible to 1) provide access to expertise and instrumentation that would otherwise not be cost effective for individual investigators, 2) facilitate exchange of ideas, and 3) encourage integrated and comprehensive research related to DNA repair and mutagenesis. In addition to the Administrative Core, which will also oversee a pilot project program and the Community Outreach and educational Program, there will be three scientific service cores which are as follows: - Molecular Biology - Protein Chemistry, Expression and Structural Analysis - Signal Transduction It is envisioned that the development of an NIEHS Center will provide a framework for conducting outstanding environmentally relevant health sciences research.