Journal
NATURE
Volume 454, Issue 7202, Pages 291-U12Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature07118
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Funding
- NIGMS NIH HHS [F32 GM078769, F32 GM078769-02, R01 GM078153-02, R01 GM078153-01, F32 GM078769-01] Funding Source: Medline
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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 similar to 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.
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