Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 7, Issue -, Pages -Publisher
WILEY
DOI: 10.1038/msb.2011.91
Keywords
cell cycle; cytokinesis; fission yeast; gene overexpression; mathematical model
Categories
Funding
- National BioResource Project (NBRP) [FY7652]
- Japan Science and Technology Agency
- Special Coordination Fund for Promoting Sciences and Technology
- Ministry of Education, Culture, Sports, Science, and Technology
- Grants-in-Aid for Scientific Research [23310140] Funding Source: KAKEN
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Cellular systems are generally robust against fluctuations of intracellular parameters such as gene expression level. However, little is known about expression limits of genes required to halt cellular systems. In this study, using the fission yeast Schizosaccharomyces pombe, we developed a genetic 'tug-of-war' (gTOW) method to assess the overexpression limit of certain genes. Using gTOW, we determined copy number limits for 31 cell-cycle regulators; the limits varied from 1 to > 100. Comparison with orthologs of the budding yeast Saccharomyces cerevisiae suggested the presence of a conserved fragile core in the eukaryotic cell cycle. Robustness profiles of networks regulating cytokinesis in both yeasts (septation-initiation network (SIN) and mitotic exit network (MEN)) were quite different, probably reflecting differences in their physiologic functions. Fragility in the regulation of GTPase spg1 was due to dosage imbalance against GTPase-activating protein (GAP) byr4. Using the gTOW data, we modified a mathematical model and successfully reproduced the robustness of the S. pombe cell cycle with the model. Molecular Systems Biology 7: 556; published online 6 December 2011; doi:10.1038/msb.2011.91
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