Chromosome Condensation in Yeast

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Cell division produces two new cells and it can only occur after the DNA in the cell has been duplicated. The two identical duplicate sets of genetic information have to be packaged into highly compact bodies called mitotic chromosomes in order for them to be accurately divided between the two new cells. This packaging of the DNA is termed chromosome condensation and without this process mitotic chromosomes fail to be distributed evenly to the new cells, resulting in cell death or abnormal cell function. Although it is a fundamental and essential biological process, the activities that perform chromosome condensation are not well understood. This project employs new methods applied to the study of chromosome condensation in a model organism, budding yeast. Budding yeast chromosomes are too small to be visualized, thus condensation cannot be examined directly. To overcome this problem, the project uses fluorescent-tagged chromosomes to visualize condensation inside living cells. The long-term goal of the project is to understand the mechanism of chromosome condensation. There are two known factors, called topoisomerase II and condensin, which contribute to chromosome condensation, but neither of these is sufficient for the process. The project will identify new factors that drive condensation and will also determine how topoisomerase II and condensin are regulated as this is not currently understood. The Specific Objectives of the project are to: (A) Identify and characterize novel chromosome condensation factors, (B) Determine the mechanisms that drive chromosome condensation, (C) Orchestrate multi-disciplinary research and training and disseminate the findings.Broader Impact:The use of yeast as a model system lends itself well to the education and training of undergraduate, graduate and post-doctoral students because it allows multi-disciplinary research that combines genetics, cell biology and biochemistry. Moreover, yeast methods and yeast genetic screens in particular are well suited to undergraduate research because of the ease of manipulation and forgiving growth properties. This project will involve a team of undergraduate students who will be trained in many aspects of yeast genetics and cell biology. A graduate student and a post-doctoral student will gain further expertise in yeast research and will gain skills in the mentoring of undergraduate students. The scientific outcomes of the project will have broad impact on the scientific community, beyond the primary goal of identifying the condensation mechanism, because the project will identify new proteins involved in several aspects of chromosome dynamics, structure and segregation.