The cyclin dependent kinase Cdk1 controls the cell cycle, which is best understood in the model organism S. cerevisiae. Research performed during the past decade has significantly improved our understanding of the molecular machinery of the cell cycle. Approximately 75 targets of Cdk1 have been identified that control critical cell cycle events, such as DNA replication and segregation, transcriptional programs and cell morphogenesis. In this review we discuss currently known targets of Cdk1 in the budding yeast S. cerevisiae and highlight the role of Cdk1 in several crucial processes including maintenance of genome stability.

The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which Sumo can regulate transcription. Although many individual substrates have been described that are sumoylated during the Sumo stress response, an emerging concept is modification of entire complexes or pathways by Sumo. This review focuses on the function and regulation of Sumo during the stress response.

Transcription factors are abundant Sumo targets, yet the global distribution of Sumo along the chromatin and its physiological relevance in transcription are poorly understood. Using Saccharomyces cerevisiae, we determined the genome-wide localization of Sumo along the chromatin. We discovered that Sumo-enriched genes are almost exclusively involved in translation, such as tRNA genes and ribosomal protein genes (RPGs). Genome-wide expression analysis showed that Sumo positively regulates their transcription. We also discovered that the Sumo consensus motif at RPG promoters is identical to the DNA binding motif of the transcription factor Rap1. We demonstrate that Rap1 is a molecular target of Sumo and that sumoylation of Rap1 is important for cell viability. Furthermore, Rap1 sumoylation promotes recruitment of the basal transcription machinery, and sumoylation of Rap1 cooperates with the target of rapamycin kinase complex 1 (TORC1) pathway to promote RPG transcription. Strikingly, our data reveal that sumoylation of Rap1 functions in a homeostatic feedback loop that sustains RPG transcription during translational stress. Taken together, Sumo regulates the cellular translational capacity by promoting transcription of tRNA genes and RPGs.

The cyclin-dependent kinase Cdk1 is best known for its function as master regulator of the cell cycle. It phosphorylates several key proteins to control progression through the different phases of the cell cycle. However, studies conducted several decades ago with mammalian cells revealed that Cdk1 also directly regulates the basal transcription machinery, most notably RNA polymerase II. More recent studies in the budding yeast Saccharomyces cerevisiae have revisited this function of Cdk1 and also revealed that Cdk1 directly controls RNA polymerase III activity. These studies have also provided novel insight into the physiological relevance of this process. For instance, cell cycle-stage-dependent activity of these complexes may be important for meeting the increased demand for various proteins involved in housekeeping, metabolism, and protein synthesis. Recent work also indicates that direct regulation of the RNA polymerase II machinery promotes cell cycle entry. Here, we provide an overview of the regulation of basal transcription by Cdk1, and we hypothesize that the original function of the primordial cell-cycle CDK was to regulate RNAPII and that it later evolved into specialized kinases that govern various aspects of the transcription machinery and the cell cycle.

The cyclin-dependent kinase Cdc28 is the master regulator of the cell cycle in Saccharomyces cerevisiae. Cdc28 initiates the cell cycle by activating cell-cycle–specific transcription factors that switch on a transcriptional program during late G1 phase. Cdc28 also has a cell-cycle–independent, direct function in regulating basal transcription, which does not require its catalytic activity. However, the exact role of Cdc28 in basal transcription remains poorly understood, and a function for its kinase activity has not been fully explored. Here we show that the catalytic activity of Cdc28 is important for basal transcription. Using a chemical-genetic screen for mutants that specifically require the kinase activity of Cdc28 for viability, we identified a plethora of basal transcription factors. In particular, CDC28 interacts genetically with genes encoding kinases that phosphorylate the C-terminal domain of RNA polymerase II, such as KIN28. ChIP followed by high-throughput sequencing (ChIP-seq) revealed that Cdc28 localizes to at least 200 genes, primarily with functions in cellular homeostasis, such as the plasma membrane proton pump PMA1. Transcription of PMA1 peaks early in the cell cycle, even though the promoter sequences of PMA1 (as well as the other Cdc28-enriched ORFs) lack cell-cycle elements, and PMA1 does not recruit Swi4/6-dependent cell-cycle box-binding factor/MluI cell-cycle box binding factor complexes. Finally, we found that recruitment of Cdc28 and Kin28 to PMA1 is mutually dependent and that the activity of both kinases is required for full phosphorylation of C-terminal domain–Ser5, for efficient transcription, and for mRNA capping. Our results reveal a mechanism of cell-cycle–dependent regulation of basal transcription.