Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2615
Zielke, N; Querings, S; Rottig, C; Lehner, C F; Sprenger, F (2008). The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. Genes and Development, 22(12):1690-1703.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Deposited On:||25 Jun 2008 09:21|
|Last Modified:||27 Nov 2013 20:03|
|Publisher:||Cold Spring Harbor Laboratory Press|
|Citations:||Web of Science®. Times Cited: 49|
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