Eukaryotic cells ensure the stable propagation of their genome by coupling each round of DNA replication (S phase) to passage through mitosis (M phase). This control is exerted at the initiation of replication, which occurs at multiple origins throughout the genome. Once an origin has initiated, reinitiation is blocked until the completion of mitosis, ensuring that DNA is replicated at most once per cell cycle. Recent studies in several organisms have suggested a model in which S- and M-phase promoting cyclin-dependent kinases prevent reinitiation by blocking the repetition of an early step in the initiation reaction. In budding yeast, this regulation is thought to involve inhibition of prereplicative complex (pre-RC) formation at origins by S and M phase-promoting Clb kinases. To date, however, there has been no direct demonstration that these kinases can perform such an important function. In this report we provide such a confirmation by showing that ectopic induction in G1 phase of a mitotic Clb, Clb2, is sufficient to inhibit DNA replication and does so by preventing pre-RC formation. This inhibition requires that Clb2 be induced before Cdc6, an initiation protein required for pre-RC formation; once pre-RCs have formed, Clb2 can no longer inhibit initiation. These results support the notion that during the normal cell cycle reassembly of the pre-RC, and hence reinitiation at an origin, is directly inhibited by S and M phase-promoting cyclin-dependent kinases.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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