Transcriptional regulation is a major controller of cell cycle transition dynamics

Alessandro Romanel, Lars Juhl Jensen, Luca Cardelli, Attila Csikász-Nagy

Research output: Contribution to journalJournal articleResearchpeer-review

12 Citations (Scopus)

Abstract

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to 'sloppy' transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences.
Original languageEnglish
JournalP L o S One
Volume7
Issue number1
Pages (from-to)e29716
ISSN1932-6203
DOIs
Publication statusPublished - 2012

Keywords

  • Cell Cycle
  • Cell Cycle Checkpoints
  • Computational Biology
  • Computer Simulation
  • Gene Expression Regulation
  • Humans
  • Kinetics
  • Models, Biological
  • Schizosaccharomyces
  • Transcription Factors
  • Transcription, Genetic

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