The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase Journal Article
| Authors: | Lee, J. K.; Seo, Y. S.; Hurwitz, J. |
| Article Title: | The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase |
| Abstract: | Previous studies in Saccharomyces cerevisiae have defined an essential role for the Dbf4-Cdc7 kinase complex in the initiation of DNA replication presumably by phosphorylation of target proteins, such as the minichromosome maintenance (Mcm) complex. We have examined the phosphorylation of the Mcm complex by the Dfp1-Hsk1 kinase, the Schizosaccharomyces pombe homologue of Dbf4-Cdc7. In vitro, the purified Dfp1-Hsk1 kinase efficiently phosphorylated Mcm2p. In contrast, Mcm2p, present in the six-subunit Mcm complex, was a poor substrate of this kinase and required Cdc23p (homologue of Mcm10p) for efficient phosphorylation. In the presence of Cdc23p, Dfp1-Hsk1 phosphorylated the Mcm2p and Mcm4p subunits of the Mcm complex. Cdc23p interacted with both the Mcm complex and Dfp1-Hsk1 by selectively binding to the Mcm4/6/7 subunits and Dfp1p, respectively. The N terminus of Cdc23p was found to interact directly with Dfp1-Hsk1 and was essential for phosphorylation of the Mcm complex. Truncated derivatives of Cdc23p that complemented the temperature-sensitive phenotype of cdc23 mutant cells also stimulated the phosphorylation of Mcm complex, implying that this activity might be a critical role of Cdc23p in vivo. These results suggest that Cdc23p participates in the activation of prereplicative complex by recruiting the Dfp1-Hsk1 kinase and stimulating the phosphorylation of the Mcm complex. |
| Keywords: | protein phosphorylation; unclassified drug; dose response; nonhuman; dna replication; cell cycle protein; phenotype; metabolism; cell cycle proteins; biological model; models, biological; protein binding; enzyme activation; enzymology; dose-response relationship, drug; enzyme activity; protein serine threonine kinase; phosphorylation; physiology; time; time factors; saccharomyces cerevisiae; protein-serine-threonine kinases; temperature; protein structure, tertiary; serodiagnosis; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; multienzyme complex; multienzyme complexes; enzyme substrate complex; protein kinase; protein tertiary structure; schizosaccharomyces; schizosaccharomyces pombe proteins; schizosaccharomyces pombe protein; genetic complementation; schizosaccharomyces pombe; genetic complementation test; scaffold protein; minichromosome maintenance protein; carboxylyase; peptide synthase; peptide synthases; precipitin tests; priority journal; article; protein cdc23; protein kinase hsk1; cdc23 protein, s cerevisiae; hsk1 protein, s pombe; carboxy-lyases; mcm1 protein |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 100 |
| Issue: | 5 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2003-03-04 |
| Start Page: | 2334 |
| End Page: | 2339 |
| Language: | English |
| DOI: | 10.1073/pnas.0237384100 |
| PUBMED: | 12604790 |
| PROVIDER: | scopus |
| PMCID: | PMC151341 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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