This application seeks partial support for a 2.5 day meeting on DNA Base Excision Repair Workshop on March 10-13, 2000 at San Luis Conference Center, Galveston, TX. The genomes of all organisms are being continuously exposed to a wide variety of genotoxic insults due to both endogenous chemicals, in particular reactive oxygen species (ROS), as well as a variety of environmental agents including UV and ionizing radiation, pollutants including carcinogenic compounds, metal ions and toxins. Many of these also induce ROS in the cell either directly or indirectly via metabolic interactions. DNA repair is ubiquitous and is essential for survival by preventing mutagenesis and carcinogenesis which arise from persistent DNA lesions. Genotoxicity of ROS has been implicated in the etiology of an ever increasing number of diseases including cancer, arthritis, and in aging. ROS-induced DNA damage, which includes oxidized base lesions and DNA strand breaks, is repaired primarily via the base excision repair (BER) pathway. Although the structure-function studies of many of the BER proteins have been investigated, it is now clear that multiple BER processes exist and may involve complex in vivo interactions. Thus these processes may require many more proteins than proposed earlier. A significant surge in interest in BER, particularly in mammalian cells, and recent observations on regulation of BER proteins have set the stage for a comprehensive and in-depth review of various aspects of BER as is planned for the Workshop. The participants will be the leaders in BER studies in the U.S. and abroad, and the goal is to stimulate interest of the next generation of scientists, including graduate students, postdocs and young faculty members in BER processes in vivo and in vitro. The total number of attendees will be approximately 125. It is planned that the proceedings of the Workshop will be published as a special issue of Prog. Nucleic Acid Res. Mol. Biol. (Acad. Press) in order to document the current results as well as hypotheses and models which should stimulate future experimental design. Thus the agenda f this meeting with a narrow and defined focus is unique, and is different from that of other recent meetings which have included broad discussions on DNA repair.
