Impaired coenzyme A synthesis in fission yeast causes defective mitosis, quiescence-exit failure, histone hypoacetylation and fragile DNA

Nakamura, Takahiro; Pluskal, Tomáš; Nakaseko, Yukinobu; Yanagida, Mitsuhiro

doi:10.1098/rsob.120117

Cited by 33 publications

(34 citation statements)

References 72 publications

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“…Consistent with this, and supporting our results, previous work showed that reduced expression of Ppc1p, the homologue of Cab2p in Schizosaccharomyces pombe, caused diminished histone acetylation (51). However, we only detected a modest decrease in the level of histone 17 / 33 acylation in the cab1 ts mutant but no in the cab3 ts mutant (Figures S6A).…”

Section: Cab4p and Cab5p Regulate The Acetylation Level Of Histone H4supporting

confidence: 82%

Cell Lysate Microarray for Mapping the Network of Genetic Regulators for Histone Marks

Cheng

Liu

Jiang

et al. 2018

Molecular & Cellular Proteomics

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SUMMARYProteins, as the major executer for cell progresses and functions, its abundance and the level of post-translational modifications, are tightly monitored by regulators.Genetic perturbation could help us to understand the relationships between genes and protein functions. Herein, to explore the impact of the genome-wide interruption on certain protein, we developed a cell lysate microarray on kilo-conditions (CLICK) with 4,837 knockout (YKO) and 322 temperature-sensitive (ts) mutant strains of yeast (Saccharomyces cerevisiae). Taking histone marks as examples, a general workflow was established for the global identification of upstream regulators. Through a single CLICK array test, we obtained a series of regulators for H3K4me3, which covers most of the known regulators in S.accharomyces. We also noted that several group of proteins that are involved in negatively regulation of H3K4me3. Further, we discovered that Cab4p and Cab5p, two key enzymes of CoA biosynthesis, play central roles in histone acylation. Because of its general applicability, CLICK array could be easily adopted to rapid and global identification of upstream protein/enzyme(s) that regulate/modify the level of a protein or the posttranslational modification of a non-histone protein.

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Section: Cab4p and Cab5p Regulate The Acetylation Level Of Histone H4supporting

confidence: 82%

Cell Lysate Microarray for Mapping the Network of Genetic Regulators for Histone Marks

Cheng

Liu

Jiang

et al. 2018

Molecular & Cellular Proteomics

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“…5a) [45]. The acs1 gene has been reported to be non-essential based on large-scale deletion analyses [30].…”

Section: Resultsmentioning

confidence: 99%

Functional and regulatory profiling of energy metabolism in fission yeast

et al. 2016

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BackgroundThe control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration.ResultsWe screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction.ConclusionsThis study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1101-2) contains supplementary material, which is available to authorized users.

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“…The first type is called ‘superhousekeeping’ (SHK) genes, as these were initially identified as essential genes by temperature-sensitive (t-s) mutants in the proliferative phase and later also shown to be required for cell quiescence [18,19,20]. The other type, called G0-specific essential, are genes identified by the use of deletion mutants.…”

Section: Introductionmentioning

confidence: 99%

Klf1, a C2H2 Zinc Finger-Transcription Factor, Is Required for Cell Wall Maintenance during Long-Term Quiescence in Differentiated G0 Phase

et al. 2013

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Fission yeast, Schizoaccharomyces pombe, is a model for studying cellular quiescence. Shifting to a medium that lacks a nitrogen-source induces proliferative cells to enter long-term G0 quiescence. Klf1 is a Krüppel-like transcription factor with a 7-amino acid Cys2His2-type zinc finger motif. The deletion mutant, ∆klf1, normally divides in vegetative medium, but proliferation is not restored after long-term G0 quiescence. Cell biologic, transcriptomic, and metabolomic analyses revealed a unique phenotype of the ∆klf1 mutant in quiescence. Mutant cells had diminished transcripts related to signaling molecules for switching to differentiation; however, proliferative metabolites for cell-wall assembly and antioxidants had significantly increased. Further, the size of ∆klf1 cells increased markedly during quiescence due to the aberrant accumulation of Calcofluor-positive, chitin-like materials beneath the cell wall. After 4 weeks of quiescence, reversible proliferation ability was lost, but metabolism was maintained. Klf1 thus plays a role in G0 phase longevity by enhancing the differentiation signal and suppressing metabolism for growth. If Klf1 is lost, S. pombe fails to maintain a constant cell size and normal cell morphology during quiescence.

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Impaired coenzyme A synthesis in fission yeast causes defective mitosis, quiescence-exit failure, histone hypoacetylation and fragile DNA

Cited by 33 publications

References 72 publications

Cell Lysate Microarray for Mapping the Network of Genetic Regulators for Histone Marks

Cell Lysate Microarray for Mapping the Network of Genetic Regulators for Histone Marks

Functional and regulatory profiling of energy metabolism in fission yeast

Klf1, a C2H2 Zinc Finger-Transcription Factor, Is Required for Cell Wall Maintenance during Long-Term Quiescence in Differentiated G0 Phase

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