WORKSHOP ON DNA BASE EXCISION REPAIR (BER) 2000

本申请寻求对2000年3月10日至13日在德克萨斯州加尔维斯顿圣路易斯会议中心举行的为期2.5天的DNA碱基切除修复研讨会会议的部分支持。由于内源性化学物质，特别是活性氧(ROS)，以及包括紫外线和电离辐射在内的各种环境因素，包括致癌化合物、金属离子和毒素在内的污染物，所有生物的基因组都不断地暴露在各种各样的遗传毒性侮辱中。其中许多还直接或间接地通过代谢相互作用在细胞内诱导ROS。DNA修复是无处不在的，对于生存来说是必不可少的，因为它可以防止因持续的DNA损伤引起的突变和癌变。ROS的遗传毒性与包括癌症、关节炎和衰老在内的越来越多的疾病的病因有关。ROS诱导的DNA损伤包括碱基氧化损伤和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-功能研究已经被研究，但现在清楚的是，存在多个BER过程，并且可能涉及复杂的体内相互作用。因此，这些过程可能需要比先前提出的更多的蛋白质。人们对BER的兴趣，特别是对哺乳动物细胞的兴趣的显著增加，以及最近对BER蛋白调控的观察，为按照讲习班的计划对BER的各个方面进行全面和深入的审查奠定了基础。参与者将是美国和国外BER研究的领军人物，目标是激发下一代科学家，包括研究生、博士后和年轻教职员工对体内和体外BER过程的兴趣。总出席人数约为125人。按照计划，讲习班的会议记录将作为Prog的特刊出版。核酸资源摩尔。比奥尔。(ACAD.Press)，以记录当前的结果以及应该刺激未来实验设计的假设和模型。因此，这次会议的议程具有狭隘和明确的重点，是独一无二的，不同于最近其他会议的议程，这些会议包括关于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.