論文 - 詳細
| RRC ID | 21935 |
|---|---|
| 著者 | Zielke N, Querings S, Rottig C, Lehner C, Sprenger F. |
| タイトル | The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. |
| ジャーナル | Genes Dev |
| Abstract |
Endoreplicating cells undergo multiple rounds of DNA replication leading to polyploidy or polyteny. Oscillation of Cyclin E (CycE)-dependent kinase activity is the main driving force in Drosophila endocycles. High levels of CycE-Cdk2 activity trigger S phase, while down-regulation of CycE-Cdk2 activity is crucial to allow licensing of replication origins. In mitotic cells relicensing in S phase is prevented by Geminin. Here we show that Geminin protein oscillates in endoreplicating salivary glands of Drosophila. Geminin levels are high in S phase, but drop once DNA replication has been completed. DNA licensing is coupled to mitosis through the action of the anaphase-promoting complex/cyclosome (APC/C). We demonstrate that, even though endoreplicating cells never enter mitosis, APC/C activity is required in endoreplicating cells to mediate Geminin oscillation. Down-regulation of APC/C activity results in stabilization of Geminin protein and blocks endocycle progression. Geminin is only abundant in cells with high CycE-Cdk2 activity, suggesting that APC/C-Fzr activity is periodically inhibited by CycE-Cdk2, to prevent relicensing in S-phase cells. |
| 巻・号 | 22(12) |
| ページ | 1690-703 |
| 公開日 | 2008-6-15 |
| DOI | 10.1101/gad.469108 |
| PII | 22/12/1690 |
| PMID | 18559483 |
| PMC | PMC2428065 |
| MeSH | Anaphase-Promoting Complex-Cyclosome Animals Animals, Genetically Modified Cdh1 Proteins Cell Cycle / genetics Cell Cycle / physiology* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Cycle Proteins / physiology Cells, Cultured Cyclin E / physiology Cyclin-Dependent Kinase 2 / physiology DNA Replication / genetics DNA Replication / physiology* DNA Replication Timing / genetics DNA Replication Timing / physiology* Drosophila / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology Geminin Gene Expression Regulation Mitosis / genetics Models, Biological Replication Origin / physiology Salivary Glands / metabolism Transfection Ubiquitin-Protein Ligase Complexes / physiology* |
| IF | 9.527 |
| 引用数 | 72 |
| WOS 分野 | GENETICS & HEREDITY DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | 6759R-3 10800R-1 10800R-2 |