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Cell Cycle-Regulated Transcription through the FHA Domain of Fkh2p and the Coactivator Ndd1p

Lookup NU author(s): Dr Aline Pic-Taylor, Professor Brian Morgan


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Recent studies in Saccharomyces cerevisiae by using global approaches have significantly enhanced our knowledge of the components involved in the transcriptional regulation of the cell cycle [1-3]. The Mcm1p-Fkh2p complex, in combination with the coactivator Ndd1p, plays an important role in the cell cycle-dependent expression of the CLB2 gene cluster during the G2 and M phases ([4-7]; see [8-10] for reviews). Fkh2p is phosphorylated in a cell cycle-dependent manner, and peak phosphorylation occurs coincidentally with maximal expression of Mcm1p-Fkh2p-dependent gene expression [6]. However, the mechanism by which this complex is activated in a cell cycle-dependent manner is unknown. Here, we demonstrate that the forkhead-associated (FHA) domain of Fkh2p directs cell cycle-regulated transcription and that the activity of this domain is dependent on the coactivator Ndd1p. Ndd1p was found to be phosphorylated in a cell cycle-dependent manner by Cdc28p-Clb2p, and, importantly, this phosphorylation event promotes interactions between Ndd1p and the FHA domain of Fkh2p. Furthermore, mutation of the FHA domain blocks these phosphorylation-dependent interactions and abolishes transcriptional activity. Our data therefore link the transcriptional activity of the FHA domain with cell cycle-dependent phosphorylation of the coactivator Ndd1p and reveal a mechanism that permits precise temporal activation of the Mcm1p-Fkh2p complex.

Publication metadata

Author(s): Darieva Z, Pic-Taylor A, Boros J, Spanos A, Geymonat M, Reece RJ, Sedgwick SG, Sharrocks AD, Morgan BA

Publication type: Article

Publication status: Published

Journal: Current Biology

Year: 2003

Volume: 13

Issue: 19

Pages: 1740-1745

ISSN (print): 0960-9822

ISSN (electronic): 1879-0445

Publisher: Cell Press


DOI: 10.1016/j.cub.2003.08.053

PubMed id: 14521842


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