Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico

Hisao Moriya, Ayako Chino, Orsolya Kapuy, Attila Csikász-Nagy, Béla Novák

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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-warg' (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.

Original languageEnglish
Article number556
JournalMolecular Systems Biology
Volume7
DOIs
Publication statusPublished - 2011

Fingerprint

Schizosaccharomyces
Schizosaccharomyces pombe
Cell Cycle
Regulator
Yeast
Computer Simulation
cell cycle
Cells
Cellular Systems
GTPase-activating proteins
yeasts
GTPase-Activating Proteins
Gene Expression
Saccharomycetales
Cytokinesis
Genes
GTP Phosphohydrolases
cytokinesis
guanosinetriphosphatase
Eukaryotic Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics
  • Information Systems
  • Applied Mathematics

Cite this

Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico. / Moriya, Hisao; Chino, Ayako; Kapuy, Orsolya; Csikász-Nagy, Attila; Novák, Béla.

In: Molecular Systems Biology, Vol. 7, 556, 2011.

Research output: Contribution to journalArticle

Moriya, Hisao ; Chino, Ayako ; Kapuy, Orsolya ; Csikász-Nagy, Attila ; Novák, Béla. / Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico. In: Molecular Systems Biology. 2011 ; Vol. 7.
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