title: Regulation of cell cycle and stress responses under nitrosative stress in Schizosaccharomyces pombe.
abstract: Nitric oxide (NO) acts as a signaling molecule in numerous physiological processes but excess production generates nitrosative stress in cells. The exact protective mechanism used by cells to combat nitrosative stress is unclear. In this study, the fission yeast Schizosaccharomyces pombe has been used as a model system to explore cell cycle regulation and stress responses under nitrosative stress. Exposure to an NO donor results in mitotic delay in cells through G2/M checkpoint activation and initiates rereplication. Western blot analysis of phosphorylated Cdc2 revealed that the G2/M block in the cell cycle was due to retention of its inactive phosphorylated form. Interestingly, nitrosative stress results in inactivation of Cdc25 through S-nitrosylation that actually leads to cell cycle delay. From differential display analysis, we identified plo1, spn4, and rga5, three cell cycle-related genes found to be differentially expressed under nitrosative stress. Exposure to nitrosative stress also results in abnormal septation and cytokinesis in S. pombe. In summary we propose a novel molecular mechanism of cell cycle control under nitrosative stress based on our experimental results and bioinformatics analysis.
authors.affiliation: Department of Biochemistry, University College of Science, Calcutta University, Kolkata 700019, West Bengal, India.
authors.forename: Uddalak
authors.initials: U
authors.lastname: Majumdar
authors.forename: Pranjal
authors.initials: P
authors.lastname: Biswas
authors.forename: Tuhin
authors.initials: T
authors.lastname: Subhra Sarkar
authors.forename: Debasis
authors.initials: D
authors.lastname: Maiti
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D048749:Cytokinesis; D004258:DNA Polymerase III / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D020690:GTPase-Activating Proteins; C491232:POL3 protein, S cerevisiae; C529495:Rga4 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D009569:Nitric Oxide; C501407:Plo1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D004258:DNA Polymerase III; C570820:Cdc25 protein, S pombe; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins; C500248:Spn4 protein, S pombe