The genetic blueprint of a cell is encoded in its DNA, which is organized into chromosomes within the cell nucleus. Cells with the same DNA but different functions are distinguished by the parts of the blueprint each uses to build the cell. These decisions are influenced by physically anchoring specific unused parts of the chromosomes to the membrane of the nucleus by an unknown mechanism. The overall goal of this research is to test the hypothesis that two recently identified fission yeast proteins, Lem2 and Man1, provide a "docking site" for the recruitment of unused DNA to the nuclear periphery, which is essential for the organization of chromosomes in the nucleus and the segregation of chromosomes as cells divide. This will be accomplished by removing the Lem2 and Man1 proteins from cells, and assessing the consequences by monitoring the position of specific chromosome regions in the nucleus and the ability of cells to segregate their chromosomes during meiosis. High-throughput genetic analysis will be used to identify components of the larger network within which Lem2 and Man1 function.
Yeast is an ideal organism in which to study chromosome organization because it is a simple experimental organism in which microscopy, molecular biology and classical genetics can be used to address this complex problem. These approaches are ideally suited to the mentoring, education and training of undergraduates, graduate students and post-doctoral fellows, including women and other groups underrepresented in the sciences, five of whom will carry out these studies. The scientific impact of this work will be an understanding of the basic mechanistic principles governing nuclear organization and chromosome segregation that are essential for fungal, animal and plant cells.
