Saccharomyces CDK1 Phosphorylates Rad53 Kinase in Metaphase, Influencing Cellular Morphogenesis

Diani, Laura; Colombelli, Claudia; Nachimuthu, Benjamin Tamilselvan; Donnianni, Roberto A.; Plevani, Paolo; Muzi-Falconi, Marco; Pellicioli, Achille

doi:10.1074/jbc.m109.048157

Cited by 18 publications

(35 citation statements)

References 25 publications

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“…On one hand, it is possible that Isc1 controls morphological functions of Rad53 function, which in turn, may control Swe1, and ultimately control Cdk1. On the other hand, Rad53 has phosphorylation targets of Cdk1, and a specific amino acid residue on Rad53 has been implicated in its role in certain aspects of morphogenesis (Diani et al 2009). It has been shown that both Swe1 and Cdk1 control HU-mediated G2/M arrest of isc1D cell sensitivity ), and we show here that they control morphological aberrations of isc1D cells under HU stress.…”

Section: Discussionsupporting

confidence: 48%

“…A third possibility is that treatment of isc1D cells with HU may also lead to Swe1 accumulation inducing Cdk1 phosphorylation, which can affect Rad53 phosphorylation. Cdk1-dependent Rad53 phosphorylation already has been implicated in morphogenesis in yeast (Diani et al 2009). All three pathways may be used simultaneously to affect cell morphology also.…”

Section: Discussionmentioning

confidence: 99%

“…Rad53 has been shown to control cellular morphology (Enserink et al , 2009Diani et al 2009). Our study shows that increasing Rad53 gene dosage decreases the morphological aberrations of isc1D cells to a large extent.…”

Section: Discussionmentioning

confidence: 99%

“…We explored the possible involvement of the Rad53 effector in this pathway for the following reasons: (1) HU and MMS activate DNA integrity checkpoints in which signals from Mrc1-Tof1-Csm3-Rad9 converge at the effector protein Rad53 (Alcasabas et al 2001;Foss 2001); (2) a reduction of cellular Rad53 concentration causes increased HU sensitivity of WT cells (Cordon-Preciado et al 2006); (3) Rad53 has been shown to control cellular morphology through Swe1 activity Smolka et al 2006;Diani et al 2009); and finally, (4) RAD9, implicated (above) in this pathway, is an activator of RAD53. To investigate the role of Rad53, we transformed either an empty vector or a vector carrying RAD53 into WT and isc1D strains.…”

Section: Role Of Rad53 In Hu Sensitivity and Morphological Aberrationmentioning

confidence: 99%

“…Log-phase cultures were adjusted to an A 600 of 0.4 before making 10-fold serial dilutions and spotting 2.5 ml each on the plates. Cells containing plasmids such as pCla6 (Diani et al 2009) were grown in SD/Leu 2 medium; SD/Leu 2 plates contained 25 or 50 mM HU.…”

Section: Growth Ratesmentioning

confidence: 99%

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Cellular Morphogenesis Under Stress Is Influenced by the Sphingolipid Pathway Gene ISC1 and DNA Integrity Checkpoint Genes in Saccharomyces cerevisiae

et al. 2011

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In Saccharomyces cerevisiae, replication stress induced by hydroxyurea (HU) and methyl methanesulfonate (MMS) activates DNA integrity checkpoints; in checkpoint-defective yeast strains, HU treatment also induces morphological aberrations. We find that the sphingolipid pathway gene ISC1, the product of which catalyzes the generation of bioactive ceramides from complex sphingolipids, plays a novel role in determining cellular morphology following HU/MMS treatment. HU-treated isc1D cells display morphological aberrations, cell-wall defects, and defects in actin depolymerization. Swe1, a morphogenesis checkpoint regulator, and the cell cycle regulator Cdk1 play key roles in these morphological defects of isc1D cells. A genetic approach reveals that ISC1 interacts with other checkpoint proteins to control cell morphology. That is, yeast carrying deletions of both ISC1 and a replication checkpoint mediator gene including MRC1, TOF1, or CSM3 display basal morphological defects, which increase following HU treatment. Interestingly, strains with deletions of both ISC1 and the DNA damage checkpoint mediator gene RAD9 display reduced morphological aberrations irrespective of HU treatment, suggesting a role for RAD9 in determining the morphology of isc1D cells. Mechanistically, the checkpoint regulator Rad53 partially influences isc1D cell morphology in a dosage-dependent manner.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Role Of Rad53 In Hu Sensitivity and Morphological Aberrationmentioning

confidence: 99%

Section: Growth Ratesmentioning

confidence: 99%

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Cellular Morphogenesis Under Stress Is Influenced by the Sphingolipid Pathway Gene ISC1 and DNA Integrity Checkpoint Genes in Saccharomyces cerevisiae

et al. 2011

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Current awareness on yeast

2010

Yeast

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In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Reviews; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals ‐ search completed 24th. Feb. 2010)

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Molecular Cytotoxicity Mechanisms of Allyl Alcohol (Acrolein) in Budding Yeast

Golla

Bandi

Tomar

2015

Chem. Res. Toxicol.

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Allyl alcohol (AA) is one of the environmental pollutants used as a herbicide and industrial chemical. AA undergoes enzymatic oxidation in vivo to form Acrolein (Acr), a highly reactive and ubiquitous environmental toxicant. The exposure to AA/Acr has detrimental effects on cells and is highly fatal. In corroboration to the current literature describing AA/Acr toxicity, this study aimed to investigate the molecular cytotoxicity mechanisms of AA/Acr using budding yeast as a eukaryotic model organism. Genome-wide transcriptome analysis of cells treated with a sublethal dose of AA (0.4 mM) showed differential regulation of approximately 30% of the yeast genome. Functional enrichment analysis of the AA transcriptome revealed that genes belong to diverse cellular processes including the cell cycle, DNA damage repair, metal homeostasis, stress response genes, ribosomal biogenesis, metabolism, meiosis, ubiquitination, cell morphogenesis, and transport. Moreover, we have identified novel molecular targets of AA/Acr through genetic screening, which belongs to oxidative stress, DNA damage repair, iron homeostasis, and cell wall integrity. This study also demonstrated the epigenetic basis of AA/Acr toxicity mediated through histone tails and chromatin modifiers. Interestingly, our study disclosed the use of pyrazole and ethanol as probable antidotes for AA intoxication. For the first time, this study also demonstrated the reproductive toxicity of AA/Acr using the yeast gametogenesis (spermatogenesis) model. Altogether, this study unravels the molecular mechanisms of AA/Acr cytotoxicity and facilitates the prediction of biomarkers for toxicity assessment and therapeutic approaches.

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Saccharomyces CDK1 Phosphorylates Rad53 Kinase in Metaphase, Influencing Cellular Morphogenesis

Cited by 18 publications

References 25 publications

Cellular Morphogenesis Under Stress Is Influenced by the Sphingolipid Pathway Gene ISC1 and DNA Integrity Checkpoint Genes in Saccharomyces cerevisiae

Cellular Morphogenesis Under Stress Is Influenced by the Sphingolipid Pathway Gene ISC1 and DNA Integrity Checkpoint Genes in Saccharomyces cerevisiae

Current awareness on yeast

Molecular Cytotoxicity Mechanisms of Allyl Alcohol (Acrolein) in Budding Yeast

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