Abstract
Oscillating gene expression is crucial for correct timing and progression through cell cycle. In Saccharomyces cerevisiae, G1 cyclins Cln1–3 are essential drivers of the cell cycle and have an important role for temporal fine-tuning. We measured time-resolved transcriptome-wide gene expression for wild type and cyclin single and double knockouts over cell cycle with and without osmotic stress. Clustering of expression profiles, peak time detection of oscillating genes, integration with transcription factor network dynamics, and assignment to cell cycle phases allowed us to quantify the effect of genetic or stress perturbations on the duration of cell cycle phases. Cln1 and Cln2 showed functional differences, especially affecting later phases. Deletion of Cln3 led to a delay of START followed by normal progression through later phases. Our data and network analysis suggest mutual effects of cyclins with the transcriptional regulators SBF and MBF.
Highlights
Eukaryotic cell cycle is a highly ordered process, which can be divided into four distinct phases during which a specific set of events take place: Cell growth (G1 and G2 phase), duplication of DNA (S phase), the segregation of DNA and the division of the nucleus (M phase), leading to cytokinesis
We found that the deletion of the earliest cyclin Cln[3] leads to a systematic shift of expression times, with an elongated G1 phase, especially under osmotic stress condition and in combination with the knockout of Cln[1], followed by a wild type like timing of the subsequent phases of the cell cycle
Taken together our results show that the correct activation of the G1 regulon and thereby induction of oscillating gene expression is strongly dependent on the G1 cyclins, each having specific roles in the adjustment of cell cycle timing
Summary
Eukaryotic cell cycle is a highly ordered process, which can be divided into four distinct phases during which a specific set of events take place: Cell growth (G1 and G2 phase), duplication of DNA (S phase), the segregation of DNA and the division of the nucleus (M phase), leading to cytokinesis. In a positive feedback loop, both cyclins contribute to further phosphorylation of Whi[5], thereby increasing the activation of MBF and SBF controlled genes and their own expression[14] Besides this self-enhancement, Cln[1] and Cln[2] phosphorylate further targets, such as the S phase inhibitor Sic[115,16], leading to its degradation and a subsequent entry into S phase in the continuing cell cycle. The G1 cyclins are, key to normal cell cycle progression and to the control of the cell cycle in stress scenarios
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