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MBC in Press, published online ahead of print September 15, 2004
Mol. Biol. Cell 10.1091/mbc.E04-04-0340

A more recent version of this article appeared on December 1, 2004
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Submitted on April 26, 2004
Revised on September 4, 2004
Accepted on September 7, 2004

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Michael Shapira,*{dagger} Eran Segal,{ddagger} and David Botstein*{dagger}{sect}

*Genetics Department, Stanford University School of Medicine, Stanford, CA 94305-5120; {ddagger}Computer Science Department, Stanford University, Stanford, CA 94305

Monitoring Editor: Trisha Davis

The effects of oxidative stress on yeast cell cycle depend on the stress-exerting agent. We studied the effects of two oxidative stress agents, hydrogen peroxide (HP) and the superoxide-generating agent Menadione (MD). We found that two small coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are sufficient to account for the difference in the effects of HP and MD on the progress of the cell cycle, namely G1 arrest with MD and an S phase delay followed by a G2/M arrest with HP. Support for this hypothesis is provided by fkh1fkh2 double mutants, which are affected by MD as we find HP affects wild-type cells. The apparent involvement of a forkhead protein in HP-induced cell cycle arrest, similar to that reported for C. elegans and human, describes a potentially novel stress-response pathway in yeast.

{sect}Present address: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.

{dagger}Corresponding authors. E-mail: mshapira{at}stanford.edu E-mail: botstein{at}princeton.edu






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