Genetic control of cellular quiescence in S. pombe

Abstract

Transition from proliferation to quiescence brings about extensive changes in cellular behavior and structure. However, the genes that are crucial for establishing and/or maintaining quiescence are largely unknown. The fission yeast Schizosaccharomyces pombe is an excellent model in which to study this problem, because it becomes quiescent under nitrogen starvation. Here, we characterize 610 temperature-sensitive mutants, and identify 33 genes that are required for entry into and maintenance of quiescence. These genes cover a broad range of cellular functions in the cytoplasm, membrane and nucleus. They encode proteins for stress-responsive and cell-cycle kinase signaling pathways, for actin-bound and osmo-controlling endosome formation, for RNA transcription, splicing and ribosome biogenesis, for chromatin silencing, for biosynthesis of lipids and ATP, for cell-wall and membrane morphogenesis, and for protein trafficking and vesicle fusion. We specifically highlight Fcp1, a CTD phosphatase of RNA polymerase II, which differentially affects the transcription of genes that are involved in quiescence and proliferation. We propose that the transcriptional role of Fcp1 is central in differentiating quiescence from proliferation.

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

“…The proteasome signals remained in the nucleus for 6 h after the removal of nitrogen (-N), when most cells had finished the second division and were competent to mate if cells with the opposite mating type existed. The nuclear proteasome was diminished at 12 h at the timing of G0 entry (6) (Fig. 1B).…”

“…1B). The level of proteasome subunit was unchanged during VEG to G0 transition, whereas the level of Cdc13 mitotic cyclin was greatly reduced (6) (Fig. 1C).…”

“…A notable mutant phenotype at 26°C was that mts3-1 divided only once and arrested after nitrogen withdrawal (Fig. 1K), whereas WT cells divided twice before arrest (6). The reason why the second division was omitted in mts3-1 is unknown.…”

“…We take advantage of this feature of fission yeast and adopt this yeast as a model organism to study the regulatory mechanisms of G0 phase. Previously, we identified seven genes required for G0 entry and 36 genes for maintenance (5,6), including regulators of transcription, chromatin dynamics, vesicle transport, and the actin cytoskeleton. However, many other factors may remain unidentified.…”

Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1

“…As it now stands, the genetics of S. pombe Fcp1 are limited to the following two points: (i) Deletion of the S. pombe fcp1 + gene is lethal (Kimura et al 2002); and (ii) screening of a fission yeast ts mutant library for conditional loss of viability upon entering quiescence (by nitrogen starvation) yielded an fcp1-ts allele with a single R223K coding change (Sajiki et al 2009). The latter finding reveals an intriguing phenotype, but is not mechanistically informative, insofar as the SpFcp1 R223K mutant is severely defective as a phosphatase in vitro (Hausmann and Shuman 2003) and the crystal structure teaches that Arg223 is not a catalytic residue, but plays a structural role in tethering the active site 170 DxDxT loop to surrounding secondary structure elements (Ghosh et al 2008).…”