Positive feedback of G1 cyclins ensures coherent cell cycle entry.
In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates multiple internal and external signals into an all-or-none decision to enter the cell cycle. Here we show that Start behaves like a switch due to systems-level feedback in the regulatory network. In contrast to current models proposing a linear cascade of ... Start activation, transcriptional positive feedback of the G1 cyclins Cln1 and Cln2 induces the near-simultaneous expression of the approximately 200-gene G1/S regulon. Nuclear Cln2 drives coherent regulon expression, whereas cytoplasmic Cln2 drives efficient budding. Cells with the CLN1 and CLN2 genes deleted frequently arrest as unbudded cells, incurring a large fluctuation-induced fitness penalty due to both the lack of cytoplasmic Cln2 and insufficient G1/S regulon expression. Thus, positive-feedback-amplified expression of Cln1 and Cln2 simultaneously drives robust budding and rapid, coherent regulon expression. A similar G1/S regulatory network in mammalian cells, comprised of non-orthologous genes, suggests either conservation of regulatory architecture or convergent evolution.
Mesh Terms:
Cell Cycle, Cyclins, Feedback, Physiological, G1 Phase, Gene Expression Regulation, Fungal, Mitosis, Phosphorylation, Regulon, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Deletion, Transcription Factors
Cell Cycle, Cyclins, Feedback, Physiological, G1 Phase, Gene Expression Regulation, Fungal, Mitosis, Phosphorylation, Regulon, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Deletion, Transcription Factors
Nature
Date: Jul. 17, 2008
PubMed ID: 18633409
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