DNA REPAIR AND MUTAGENESIS

申请资金用于支持美国科学家参加由美国微生物学会主办的题为“DNA修复和突变：机制、控制和生物学后果”的会议。这次会议将于1999年11月1日至7日在南卡罗来纳希尔顿黑德的威斯汀酒店举行，会议将汇集DNA修复和诱变领域的各个分支学科。自1974年以来，这种类型的会议大约每4年举行一次，并在这一令人兴奋的研究领域的发展中发挥了关键作用。预计出席人数约为500人，会议场地的选择和设计都经过了仔细的考虑，这样与会者就能享受到通常只有在小型会议（如戈登会议）上才能找到的非正式互动环境。会议将是国际性的，但已经设计了鼓励年轻研究者、博士后研究员和研究生参与的机制。会议将讨论的DNA修复和诱变领域的最新发现与人类健康直接相关，特别是与癌症、衰老、人类遗传疾病以及包括活性氧在内的环境诱变剂和致癌物构成的威胁直接相关。例如，HNPCC（遗传性非息肉病性结肠癌）基因（编码错配修复成分）的突变会破坏基因组的稳定性并增加癌症发病率。bloom（极端癌症易感性）和Werner's综合征（过早衰老）基因都被发现编码大肠杆菌RecQ解旋酶家族的蛋白质，为探索癌症易感性和衰老的潜在机制打开了新的大门。本文将讨论色素性干皮病、柯凯因病、共济失调毛细血管扩张症和奈梅亨断裂综合征中DNA修复/检查点缺陷的性质及其与人类疾病的相关性。这些发现背后的基础科学将被深入探讨，主题包括DNA修复蛋白的晶体结构、多蛋白DNA修复系统的生物化学、细胞对DNA损伤反应的遗传分析、DNA损伤检查点控制系统的分析。

Funds are requested to support the participation of U.S. scientists in a meeting entitled "DNA Repair and Mutagenesis: Mechanism, Control, and Biological Consequences" that will be sponsored by the American Society for Microbiology. This meeting, which will be held at the Westin Hotel, Hilton Head, South Carolina, November 1-7, 1999, will bring together the various sub-disciplines that collectively comprise the field of DNA Repair and Mutagenesis. Conferences of this type have been held at approximately 4-year intervals since 1974 and have played a critical role in the development of this exciting area of research. Attendance is expected to be ca. 500 and careful thought has been given to the choice of site and design of the program so that the participants will be able to enjoy the type of informal interactive environment normally found only at smaller meetings such as Gordon Conferences. The meeting will be international in scope but mechanisms have been devised to encourage the participation of young investigators, postdoctoral fellows, and graduate students. Recent discoveries in the field of DNA Repair and Mutagenesis to be discussed at the meeting have direct relevance to human health, particularly to cancer, aging, human genetic diseases, and the threats posed by environmental mutagens and carcinogens including reactive oxygen species. For example, mutation in the HNPCC (hereditary nonpolyposis colon cancer) genes (encode components of mismatch repair), destabilize the genome and increase cancer incidence. The Blooms (extreme cancer proneness) and the Werner's syndrome (premature aging) genes both have been found to encode proteins of he E. coli RecQ helicase family, opening new doors for exploring the mechanisms underlying cancer susceptibility and aging. The nature of DNA repair/checkpoint defects in Xeroderma pigmentosum, Cockayne, Ataxia telangiectasia, and the Nijmegen breakage syndrome and their relevance to human disease will be discussed. The fundamental science underlying these discoveries will be covered in depth with topics ranging from crystal structure of DNA repair proteins, to the biochemistry of multi protein DNA repair systems, to genetic analyses of cellular responses to DNA damage, to analysis of DNA damage checkpoint control systems.