Abstract
Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCFGrr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a genuine paralog of Whi5. In fact, both proteins collaborate in Start repression bringing to light that yeast cells, as occurs in mammalian cells, rely on the combined action of multiple transcriptional repressors to block Start transition.
Highlights
Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division
It involves the activation by specific cyclin-dependent kinase (CDK) kinases of a transcriptional program involving hundred of genes[3], which provides the coherent expression of key cell cycle regulators and the cellular machineries required for the early events of the cell cycle
Our results demonstrate that Whi[7] is an unstable cell cycle regulated protein that acts as a genuine paralog of Whi[5] repressing the Start transcriptional program
Summary
Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. Our results demonstrate that Whi[7] is a genuine paralog of Whi[5] Both proteins collaborate in Start repression bringing to light that yeast cells, as occurs in mammalian cells, rely on the combined action of multiple transcriptional repressors to block Start transition. The major point in cell cycle control occurs at the end of G1 phase in a process called Start in yeast and Restriction Point in mammalian cells[2] At this stage, cells decide to initiate or not a new round of cell division. Molecular strategy is extraordinarily well conserved between yeast and mammals It involves the activation by specific CDK kinases of a transcriptional program involving hundred of genes[3], which provides the coherent expression of key cell cycle regulators and the cellular machineries required for the early events of the cell cycle. Failure to proper regulate cell cycle entry can result in abnormal division and lead to cancer[4]
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