Disruption of yeast forkhead-associated cell cycle transcription by oxidative stress.
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.
Shapira
Michael
M
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. mshapira@stanford.edu
Segal
Eran
E
Botstein
David
D
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D024483:Vitamin K 3 / Q000494:pharmacology
D018797:Cell Cycle Proteins; C464906:Fkh1 protein, S cerevisiae; C464958:Fkh2 protein, S cerevisiae; D051858:Forkhead Transcription Factors; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D024483:Vitamin K 3; D006861:Hydrogen Peroxide