Abstract

Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable the cyclic behavior of dividing cells. This transcriptional network has been studied in Saccharomyces cerevisiae (budding yeast) and elsewhere. To provide more perspective on these regulatory mechanisms, we have used microarrays to measure gene expression through the cell cycle of Schizosaccharomyces pombe (fission yeast). The 750 genes with the most significant oscillations were identified and analyzed. There were two broad waves of cell cycle transcription, one in early/mid G2 phase, and the other near the G2/M transition. The early/mid G2 wave included many genes involved in ribosome biogenesis, possibly explaining the cell cycle oscillation in protein synthesis in S. pombe. The G2/M wave included at least three distinctly regulated clusters of genes: one large cluster including mitosis, mitotic exit, and cell separation functions, one small cluster dedicated to DNA replication, and another small cluster dedicated to cytokinesis and division. S. pombe cell cycle genes have relatively long, complex promoters containing groups of multiple DNA sequence motifs, often of two, three, or more different kinds. Many of the genes, transcription factors, and regulatory mechanisms are conserved between S. pombe and S. cerevisiae. Finally, we found preliminary evidence for a nearly genome-wide oscillation in gene expression: 2,000 or more genes undergo slight oscillations in expression as a function of the cell cycle, although whether this is adaptive, or incidental to other events in the cell, such as chromatin condensation, we do not know.

Highlights

  • The yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae are excellent organisms for the study of the cell division cycle

  • In S. pombe, when cells reach a critical size, the Cdc2 protein kinase is activated both by cyclin binding and by Cdc25 phosphatase removal of the inhibitory phosphate from tyr15 of Cdc2, and this leads to mitosis

  • Rustici et al [7] have pointed out several differences between the cell cycles of S. pombe and S. cerevisiae, we find that there are striking similarities, suggesting deeply conserved mechanisms

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Summary

Introduction

The yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae are excellent organisms for the study of the cell division cycle. Both yeasts have many well-characterized cell division cycle (cdc) mutants [1,2,3,4,5], and both have a long history of genetic and molecular cell cycle studies. They diverged more than 1 billion years ago, and have many lifestyle differences. A cryptic size control appears in G1 phase; that is, a G1 phase appears and becomes longer as growth rate becomes slower

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