Structure and Function of Telomerase Proteins

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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.