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Vol. 15, Issue 12, 5659-5669, December 2004

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

Michael Shapira ^* , Eran Segal  , and David Botstein ^*  ||

^* Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305; Department of Computer Science, Stanford University, Stanford, CA 94305

Submitted April 26, 2004; Revised September 4, 2004; Accepted September 7, 2004
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 Caenorhabditis elegans and human, describes a potentially novel stress response pathway in yeast.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Present address: Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10021;

^|| Present address: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544.

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

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