CDC28 phosphorylates Cac1p and regulates the association of chromatin assembly factor i with chromatin
| Autor: | Pierre Thibault, Zhiying You, Alain Verreault, Marlene Gharib, Krassimir Yankulov, Hisao Masai, Naoko Kakusho, Erin Drury, Daniel Jeffery, Brandon A. Wyse, Michael Weinreich |
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| Rok vydání: | 2015 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins Molecular Sequence Data Cell Cycle Proteins Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Chromatin remodeling S Phase Proliferating Cell Nuclear Antigen Nucleosome Amino Acid Sequence Gene Silencing Chromatin Assembly Factor-1 Phosphorylation Molecular Biology Cyclin-dependent kinase 1 DNA clamp Chromatin Assembly Factor I Cell Biology Telomere Chromatin Assembly and Disassembly Molecular biology Chromatin Proliferating cell nuclear antigen Mutation biology.protein CDC28 Protein Kinase S cerevisiae Protein Binding Reports Developmental Biology |
| Zdroj: | Cell Cycle. 14:74-85 |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | Chromatin Assembly Factor I (CAF-I) plays a key role in the replication-coupled assembly of nucleosomes. It is expected that its function is linked to the regulation of the cell cycle, but little detail is available. Current models suggest that CAF-I is recruited to replication forks and to chromatin via an interaction between its Cac1p subunit and the replication sliding clamp, PCNA, and that this interaction is stimulated by the kinase CDC7. Here we show that another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA. Mutations in the Cac1p-phosphorylation sites of CDC28 but not of CDC7 substantially reduce the in vivo phosphorylation of Cac1p. However, mutations in the putative CDC7 target sites on Cac1p reduce its stability. The association of CAF-I with chromatin is impaired in a cdc28–1 mutant and to a lesser extent in a cdc7–1 mutant. In addition, mutations in the Cac1p-phosphorylation sites by both CDC28 and CDC7 reduce gene silencing at the telomeres. We propose that this phosphorylation represents a regulatory step in the recruitment of CAF-I to chromatin in early S phase that is distinct from the association of CAF-I with PCNA. Hence, we implicate CDC28 in the regulation of chromatin reassembly during DNA replication. These findings provide novel mechanistic insights on the links between cell-cycle regulation, DNA replication and chromatin reassembly. |
| Databáze: | OpenAIRE |
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