1. Department of Biochemistry, University of Washington, Seattle, Washington 98195-7350 , USA
2. Department of Genetics, Stanford University Medical Centre, Stanford, California 94306-5120, USA
3. Graduate Program in Genetics, State University of New York, Stony Brook, New York 11794-5215, USA
4. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
5. Department of Biochemistry, Stanford University Medical Centre, Stanford, California 94306-5428, USA
6. Present address: Mayo Clinic, Department of Immunology, Rochester, Minnesota 55906, USA.

Correspondence to: Bruce Futcher⁵ Correspondence and requests for materials should be addressed to B.F. (e-mail: Email: futcher@cshl.org).

Abstract

There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell-cycle regulated^{1, 2}. Some of these form clusters of co-regulated genes¹. The 'CLB2' cluster contains 33 genes whose transcription peaks early in mitosis, including CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis¹. Here we find that the genes in this cluster lose their cell cycle regulation in a mutant that lacks two forkhead transcription factors, Fkh1 and Fkh2. Fkh2 protein is associated with the promoters of CLB2, SWI5 and other genes of the cluster. These results indicate that Fkh proteins are transcription factors for the CLB2 cluster. The fkh1 fkh2 mutant also displays aberrant regulation of the 'SIC1' cluster¹, whose member genes are expressed in the M–G1 interval and are involved in mitotic exit. This aberrant regulation may be due to aberrant expression of the transcription factors Swi5 and Ace2, which are members of the CLB2 cluster and controllers of the SIC1 cluster. Thus, a cascade of transcription factors operates late in the cell cycle. Finally, the fkh1 fkh2 mutant displays a constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help control the switch to this mode of growth.