Structure and Function of Telomerase Proteins

端粒酶是一种酶复合体，它复制染色体末端的DNA，并保护DNA不被降解。如果没有端粒酶，染色体在每次复制时(即每次细胞分裂时)都会变短。这个项目将研究端粒酶中蛋白质的结构、功能和动力学，这些蛋白质对于端粒酶的正确功能是必不可少的。该项目将增进对细胞衰老的理解，并为研究生和博士后研究员提供结构生物学和生物物理学方面的跨学科培训。鼓励女性和少数族裔从事科学事业将通过扩展到高中、通过指导本科生和博士后研究员研究以及通过加州大学洛杉矶分校城市实验室计划来实现。端粒酶是一种RNA-蛋白质复合体(RNP)，其功能是作为一种特殊的逆转录酶来延长线性染色体的3‘端，是细胞衰老和干细胞更新的关键决定因素。本研究将结合核磁共振、X射线结晶学、电子显微镜和生物化学等方法，对四膜虫端粒酶辅助蛋白的结构和功能进行研究。拟议的结构研究将整合现有的关于端粒酶和端粒结合蛋白的信息，并为端粒酶全酶的组装和相互作用提供新的见解。本项目中使用的统一结构生物学方法将适用于其他蛋白质复合体和RNPs的研究。

Telomerase is an enzyme complex that copies the DNA at the very ends of chromosomes and also protects the DNA from degradation. Without telomerase, chromosomes would get shorter every time they were copied (i.e. at every cell division). This project will investigate the structure, function, and dynamics of proteins in telomerase that are essential for its correct function. The project will advance understanding of cell aging and provide interdisciplinary training for graduate students and postdoctoral fellows in structural biology and biophysics. Encouragement to women and minorities to pursue careers in science will be pursued through outreach to high schools, by mentoring undergraduate students and postdoctoral fellows in research, and through the UCLA CityLab program. Telomerase is an RNA-protein complex (RNP) that functions as a specialized reverse transcriptase to extend the 3' ends of linear chromosomes and is a critical determinant of cellular aging and stem cell renewal. This research project will investigate the structure and function of telomerase accessory proteins in Tetrahymena using an integrative structural biology approach that combines NMR, X-ray crystallography, electron microscopy, and biochemical methods. The proposed structural studies will integrate existing information on telomerase and telomere binding proteins and provide new insights into assembly and interactions of the telomerase holoenzyme. The unified approach to structural biology used in this project will be applicable to the study of other protein complexes and RNPs.