Regulation of cell cycle and stress responses under nitrosative stress in Schizosaccharomyces pombe

Uddalak Majumdar, Pranjal Biswas, Tuhin Subhra Sarkar, Debasis Maiti, Sanjay Ghosh

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2186-2200
Number of pages15
JournalFree Radical Biology and Medicine
Volume52
Issue number11-12
DOIs
StatePublished - Jun 1 2012

Keywords

  • Cdc25
  • Cytokinesis defect
  • Free radicals
  • G2/M block
  • S-nitrosylation
  • S. pombe cell cycle

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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