Cantwell, Helena Rose; (2018) Nuclear Size Control and Homeostasis in Fission Yeast. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Despite it being recognised as a problem worthy of consideration over a century ago, we have little mechanistic understanding of how the size of a cell’s nucleus is determined. The simply shaped fission yeast Schizosaccharomyces pombe is genetically tractable and undergoes a closed mitosis, making it a useful system in which to probe mechanisms of nuclear size control. In S. pombe cells, nuclear volume scales with cell volume, and not DNA content, across a wide range of cell volumes and throughout the cell cycle, maintaining a constant nuclear volume to cell volume (N/C) ratio. This thesis explores the mechanisms by which this scaling is achieved, using physiological, genetic and biochemical approaches. N/C ratio is perturbed and resultant nuclear and cellular growth rates of individual cells are assessed. N/C ratio homeostasis is observed. Both high and low aberrant N/C ratios correct rapidly in individual cells. Analysis of the kinetics of N/C ratio recovery is carried out and mathematical models of nuclear size control are proposed. To identify molecular components and biological processes with roles in nuclear size control mechanisms, a genetic screen for deletion mutants with aberrant nuclear size and biochemical analysis of a nuclear size mutant are carried out. Ribosome biogenesis, RNA processing and nucleocytoplasmic transport are all implicated in nuclear size control.

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