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Published April 7, 2016 | Supplemental Material
Journal Article Open

The CDK-APC/C Oscillator Predominantly Entrains Periodic Cell-Cycle Transcription

Abstract

Throughout cell-cycle progression, the expression of multiple transcripts oscillate, and whether these are under the centralized control of the CDK-APC/C proteins or can be driven by a de-centralized transcription factor (TF) cascade is a fundamental question for understanding cell-cycle regulation. In budding yeast, we find that the transcription of nearly all genes, as assessed by RNA-seq or fluorescence microscopy in single cells, is dictated by CDK-APC/C. Three exceptional genes are transcribed in a pulsatile pattern in a variety of CDK-APC/C arrests. Pursuing one of these transcripts, the SIC1 inhibitor of B-type cyclins, we use a combination of mathematical modeling and experimentation to provide evidence that, counter-intuitively, Sic1 provides a failsafe mechanism promoting nuclear division when levels of mitotic cyclins are low.

Additional Information

© 2016 Elsevier Inc. Received: August 13, 2015; Revised: December 22, 2015; Accepted: February 22, 2016; Published: April 7, 2016. S.J.R. thanks Nahal Mansouri for insightful discussions and Aleeza Kazmi for help with image processing. The work was supported by NIH grant 5RO1-GM078153-07 to F.R.C., NRSA Training Grant CA009673-36A1, and Merck and Simons Foundation Postdoctoral Fellowships to S.J.R. Author Contributions: Conceptualization, S.J.R. and F.R.C.; Methodology, Writing, Analysis, S.J.R., K.P., and F.R.C.; Investigation, S.J.R., K.P., A.O., and C.O.

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