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

Zoulfia Darieva, Aline Pic-Taylor, Joanna Boros, Adonis Spanos, Marco Geymonat, Richard J. Reece, Steven G. Sedgwick, Andrew D. Sharrocks, Brian A. Morgan

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1740-1745
Number of pages5
JournalCurrent Biology
Issue number19
Publication statusPublished - 30 Sept 2003


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