Regulation of the anaphase-promoting complex by pseudosubstrate inhibition

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Research Project Description. The process of cell division, by which a single parent cell gives rise to two identical daughter cells, is amazingly complex. At its core are the duplication of the cell's entire genome and the accurate distribution of one intact copy of the genome to each of the two daughter cells. Remarkably, almost all non-bacterial species use the same basic machinery and regulatory controls to achieve cell division. How the complex steps involved in cell division are regulated is still only partially understood. In this project, budding yeast will be used as a simple model system to study one essential component of cell division control, regulated protein destruction. The project aims to understand how a key enzyme responsible for protein destruction during cell division is activated and inactivated, and the mechanism by which it specifically recognizes its targets. By using the yeast model system, a broad array of molecular techniques spanning the fields of cell biology, genetics, biochemistry, and biophysics will be applied to achieve the aims. The project will help advance the general understanding of molecular mechanisms of 1) cell division control, and 2) regulated protein destruction.Broader Impact. The research project is associated with graduate and undergraduate programs in biochemistry. A major focus is education and training of students in critical thinking and the scientific method, essential skills for future careers as independent research scientists and important skills for any science-related career. A secondary focus is development of research skills in a broad array of fundamental molecular biological techniques that will prepare students for a variety of research-related careers. Finally, a third goal is development of effective scientific communication skills. The culmination of this goal is presentation of research results at national scientific meetings by students and publication of research papers in peer-reviewed scientific journals. In summary, this project will help train the next generation of research scientists and contribute to the public collection of basic biological knowledge.