Nuclear Division in Fission Yeast

Baylor College Of Medicine, Houston TX

Investigators

Abstract

In order for a cell to proliferate it must duplicate its genome, separate the two sets of chromosomes at mitosis, and then distribute one set into each of the two daughter cells. In eukaryotic cells the genome is separated from the rest of the cell by the nuclear envelope. In animal cells the nuclear envelope is degraded at mitosis and then reformed around each of the two sets of chromosomes. This orderly breakdown and re-assembly of the nuclear envelope at every mitosis depends on the nuclear lamins, which form a meshwork of intermediate filaments that is anchored to the inner nuclear envelope by means of integral membrane proteins. In contrast, the yeast nuclear envelope remains intact throughout the cell cycle. As the intra-nuclear mitotic spindle elongates, the nucleus of the fission yeast, Schizosaccharomyces pombe, changes from round to oblong to dumbbell-shaped before separating into two individual nuclei, each of which contains a full complement of chromosomes. It is not known how the shape or structure of the yeast nucleus is maintained or how nuclear division is accomplished. In the fully sequenced genomes of budding or fission yeast, there are no genes that encode lamin-like proteins. The goal of this project is to identify and characterize the proteins that are required for nuclear structure and function in the fission yeast, S. pombe. This will be accomplished using two complementary strategies: genetic screens to identify proteins that are required for proper nuclear division and a genomic/proteomic approach in which candidate proteins that localize to the nuclear envelope and are required for nuclear division will be characterized. These studies will answer long-standing questions regarding the structural organization of yeast nuclei and differences between cells that break down their nuclear envelope at mitosis and those that do not. This work will have more general applications for understanding how membranes change shape and topology. In these respects, nuclear division in yeast has similarities to vesicle budding from membrane-bound organelles and to the process by which many types of cells and organelles divide. The project will provide research training at three levels: undergraduate, graduate and postdoctoral.