Dynamics of SIN Asymmetry Establishment

Archana Bajpai, Anna Feoktistova, Jun Song Chen, Dannel McCollum, Masamitsu Sato, Rafael E. Carazo-Salas, Kathleen L. Gould, Attila Csikász-Nagy*


研究成果: Article査読

10 被引用数 (Scopus)


Timing of cell division is coordinated by the Septation Initiation Network (SIN) in fission yeast. SIN activation is initiated at the two spindle pole bodies (SPB) of the cell in metaphase, but only one of these SPBs contains an active SIN in anaphase, while SIN is inactivated in the other by the Cdc16-Byr4 GAP complex. Most of the factors that are needed for such asymmetry establishment have been already characterized, but we lack the molecular details that drive such quick asymmetric distribution of molecules at the two SPBs. Here we investigate the problem by computational modeling and, after establishing a minimal system with two antagonists that can drive reliable asymmetry establishment, we incorporate the current knowledge on the basic SIN regulators into an extended model with molecular details of the key regulators. The model can capture several peculiar earlier experimental findings and also predicts the behavior of double and triple SIN mutants. We experimentally tested one prediction, that phosphorylation of the scaffold protein Cdc11 by a SIN kinase and the core cell cycle regulatory Cyclin dependent kinase (Cdk) can compensate for mutations in the SIN inhibitor Cdc16 with different efficiencies. One aspect of the prediction failed, highlighting a potential hole in our current knowledge. Further experimental tests revealed that SIN induced Cdc11 phosphorylation might have two separate effects. We conclude that SIN asymmetry is established by the antagonistic interactions between SIN and its inhibitor Cdc16-Byr4, partially through the regulation of Cdc11 phosphorylation states.

ジャーナルPLoS Computational Biology
出版ステータスPublished - 2013 7月

ASJC Scopus subject areas

  • 生態、進化、行動および分類学
  • モデリングとシミュレーション
  • 生態学
  • 分子生物学
  • 遺伝学
  • 細胞および分子神経科学
  • 計算理論と計算数学


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