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.
Duke Scholars
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- Transcription Factors
- Sequence Deletion
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Repressor Proteins
- Regulon
- Phosphorylation
- Mitosis
- General Science & Technology
- Gene Expression Regulation, Fungal
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription Factors
- Sequence Deletion
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Repressor Proteins
- Regulon
- Phosphorylation
- Mitosis
- General Science & Technology
- Gene Expression Regulation, Fungal