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Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein


Polo kinases have crucial conserved functions in controlling the eukaryotic cell cycle through orchestrating several events during mitosis1,2. An essential element of cell cycle control is exerted by altering the expression of key regulators3. Here we show an important function for the polo kinase Cdc5p in controlling cell-cycle-dependent gene expression that is crucial for the execution of mitosis in the model eukaryote Saccharomyces cerevisiae. In particular, we find that Cdc5p is temporally recruited to promoters of the cell-cycle-regulated CLB2 gene cluster, where it targets the Mcm1p–Fkh2p–Ndd1p transcription factor complex, through direct phosphorylation of the coactivator protein Ndd1p. This phosphorylation event is required for the normal temporal expression of cell-cycle-regulated genes such as CLB2 and SWI5 in G2/M phases. Furthermore, severe defects in cell division occur in the absence of Cdc5p-mediated phosphorylation of Ndd1p. Thus, polo kinase is required for the production of key mitotic regulators, in addition to previously defined roles in controlling other mitotic events.

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Figure 1: Cdc5p is recruited to CLB2 gene cluster promoters and phosphorylates Ndd1p.
Figure 2: Ndd1p is phosphorylated at Ser 85 by Cdc5p.
Figure 3: Ser 85 of Ndd1p is required for several cell-cycle-dependent processes.
Figure 4: Ser 85 of Ndd1p is required for normal promoter recruitment and CLB2 gene cluster expression.

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We thank A. Clancy for technical assistance; I. Hagan, P. March, M. Jackson and G. Pereira for advice; A. Whitmarsh, S.-H. Yang and members of our laboratories for comments on the manuscript and helpful discussions; and M. Walberg, U. Surana, G. Pereira and D. Lydall for reagents. This work was supported by Cancer Research UK, the BBSRC, the MRC and the Wellcome Trust.

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Correspondence to Brian A. Morgan or Andrew D. Sharrocks.

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Supplementary Notes

This file contains Supplementary Methods and Supplementary Figure Legends. (DOC 75 kb)

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Supplementary Data

This is a list of the key genes and proteins used in this study. (DOC 23 kb)

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Darieva, Z., Bulmer, R., Pic-Taylor, A. et al. Polo kinase controls cell-cycle-dependent transcription by targeting a coactivator protein . Nature 444, 494–498 (2006).

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