WORKSHOP ON DNA BASE EXCISION REPAIR (BER) 2000

本申请寻求对2000年3月10-13日在San Luis Conference Center，加尔维斯顿，TX举行的为期2.5天的DNA碱基切除修复研讨会的部分支持。 由于内源性化学物质，特别是活性氧（ROS），以及各种环境因素，包括紫外线和电离辐射，污染物，包括致癌化合物，金属离子和毒素，所有生物体的基因组不断暴露于各种各样的遗传毒性损伤。 其中许多还通过代谢相互作用直接或间接诱导细胞中的ROS。 DNA修复是普遍存在的，并且通过防止由持续的DNA损伤引起的诱变和致癌而对生存至关重要。 ROS的遗传毒性与越来越多的疾病（包括癌症、关节炎和衰老）的病因有关。 ROS诱导的DNA损伤，包括氧化碱基损伤和DNA链断裂，主要通过碱基切除修复（BER）途径修复。 虽然许多BER蛋白的结构-功能研究已经被调查，现在很清楚，多个BER过程存在，并可能涉及复杂的体内相互作用。 因此，这些过程可能需要比以前提出的更多的蛋白质。对BER，特别是哺乳动物细胞的兴趣大增，以及最近对BER蛋白质调节的观察，为计划在讲习班上全面深入审查BER的各个方面奠定了基础。 参与者将成为美国和国外BER研究的领导者，目标是激发下一代科学家的兴趣，包括研究生，博士后和年轻的教职员工在体内和体外BER过程中。 与会者总数约为125人。 计划将讲习班的记录作为《方案》的特刊出版。核酸研究分子量生物学（Acad.出版社），以记录目前的结果以及假设和模型，应刺激未来的实验设计。因此，这次会议的议程是独特的，重点是狭窄和明确的，与最近的其他会议不同，这些会议包括对DNA修复的广泛讨论。

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.