The final step of cell division is the physical separation of daughter cells by cytokinesis. This process is crucial for growth of all organisms from bacteria to humans. The cell cycle and cytokinesis must but must be properly regulated to enable growth and development as well as to prevent division errors. Cytokinetic failure leads to aberrant ploidy increases, which are thought to contribute to tumorigenesis. Decades of research have been spent elucidating the mechanisms governing this essential process; however, many aspects of its regulation remain poorly understood. Multiple lines of evidence suggest the existence of a ring checkpoint governing constriction of the conserved contractile ring during cytokinesis. I will use the model yeast Schizosaccharomyces pombe to identify proteins involved in each component of the constriction checkpoint and determine how their interactions regulate actomyosin ring constriction. The components of this checkpoint and the mechanisms by which they interact with and regulate the contractile ring and the enzymes synthesizing the cell wall remain unknown. The conservation of this process suggests that proteins and mechanisms are likely similar to cytokinetic regulation in animal cells, in which interactions with the extracellular matrix and neighboring cells providing analogous inputs to the cell wall in fission yeast. In the proposed work, I will identify the components and elucidate the mechanisms that trigger constriction and septum ingression upon checkpoint satisfaction (Aim 1), put a brake on constriction of the contractile ring before it is complete (Aim 2), and sense the completion of contractile ring assembly (Aim 3).
A comprehensive understanding of the mechanisms by which cells successfully grow and divide is essential to our ability to combat genetic disorders, microbial diseases, and cancer progression. I will determine the components and mechanisms of a poorly-characterized checkpoint in fission yeast that governs cytokinetic ring constriction. This work will provide valuable insight into the regulation of cellular division, required for the propagation of all cells.
