[Show abstract][Hide abstract] ABSTRACT: Activation of the CLB gene cluster through the assembly of Mcm1p-Fkh2p complexes at target promoters is essential for mitotic entry and transition through M phase. We show that the activation of this mitotic transcriptional program is dependent on the recruitment of Ndd1p, a coactivator that performs its essential function by acting through Fkh2p. Although an essential gene, NDD1 is dispensable in cells expressing a truncated form of Fkh2p lacking its C terminus. When phosphorylated on T319, Ndd1p is recruited to CLB cluster promoters by association with the forkhead-associated (FHA) domain of Fkh2p. Substitution of T319 for alanine significantly reduces recruitment of Ndd1p, resulting in loss of normal transcriptional regulation, severe impairment of cell growth, and a budding defect reminiscent of cells with a Cdk-Clb kinase deficiency. Finally, we show that phosphorylation of T319 and recruitment of Ndd1p to CLB2 and SWI5 promoters is dependent on Cdc28-Clb kinase activity. These data provide a model describing the activation of G2/M transcription through the phosphorylation of Ndd1p by Cdc28-Clb kinase activity.
Genes & Development 08/2003; 17(14):1789-802. · 12.64 Impact Factor