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Disruption of yeast forkhead-associated cell cycle transcription by oxidative stress

Michael Shapira1, Eran Segal, David Botstein

  • 1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. mshapira@stanford.edu

Molecular Biology of the Cell
|September 17, 2004
PubMed

Insights

Oxidative stress impacts yeast cell cycles differently based on the agent. Hydrogen peroxide causes S/G2/M arrest, while menadione induces G1 arrest, explained by specific gene groups.

Area of Science:

  • Cell biology
  • Molecular biology
  • Genetics

Background:

  • Oxidative stress significantly influences cellular processes, including the cell cycle.
  • Different oxidative agents can elicit distinct cellular responses.
  • Understanding these responses is crucial for comprehending cellular defense mechanisms.

Purpose of the Study:

  • To investigate the differential effects of hydrogen peroxide (HP) and menadione (MD) on the yeast cell cycle.
  • To identify the molecular mechanisms underlying these distinct responses.
  • To explore the role of transcription regulatory complexes in mediating stress-induced cell cycle arrest.

Main Methods:

  • Utilizing yeast as a model organism.
  • Employing hydrogen peroxide (HP) and menadione (MD) as oxidative stress agents.
  • Analyzing gene expression patterns and cell cycle progression.
  • Investigating the function of the Mcm1-Fkh2-Ndd1 transcription complex and forkhead proteins.

Main Results:

  • Hydrogen peroxide (HP) induced an S phase delay followed by G2/M arrest.
  • Menadione (MD) caused a G1 arrest.
  • Two coexpressed gene groups regulated by the Mcm1-Fkh2-Ndd1 complex were sufficient to explain the differential cell cycle effects.
  • fkh1fkh2 double mutants exhibited MD-like responses, suggesting a role for forkhead proteins in HP-induced arrest.

Conclusions:

  • The Mcm1-Fkh2-Ndd1 transcription complex plays a key role in mediating distinct yeast cell cycle responses to different oxidative stress agents.
  • A potentially novel stress response pathway involving forkhead proteins in HP-induced cell cycle arrest is identified in yeast.
  • Findings suggest conserved mechanisms of oxidative stress response across species, including humans.

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