Transcriptional regulation is a major controller of cell cycle transition dynamics
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Transcriptional regulation is a major controller of cell cycle transition dynamics. / Romanel, Alessandro; Jensen, Lars Juhl; Cardelli, Luca; Csikász-Nagy, Attila.
In: P L o S One, Vol. 7, No. 1, 2012, p. e29716.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Transcriptional regulation is a major controller of cell cycle transition dynamics
AU - Romanel, Alessandro
AU - Jensen, Lars Juhl
AU - Cardelli, Luca
AU - Csikász-Nagy, Attila
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Cell Cycle
KW - Cell Cycle Checkpoints
KW - Computational Biology
KW - Computer Simulation
KW - Gene Expression Regulation
KW - Humans
KW - Kinetics
KW - Models, Biological
KW - Schizosaccharomyces
KW - Transcription Factors
KW - Transcription, Genetic
U2 - 10.1371/journal.pone.0029716
DO - 10.1371/journal.pone.0029716
M3 - Journal article
C2 - 22238641
VL - 7
SP - e29716
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
ER -
ID: 40290850