Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.
Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.
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DOI：
10.1038/ncomms2859
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发表时间：
2013
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
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Geminin 是 DNA 复制的重要因子，直接与许可因子 Cdt1 结合并抑制复制前复合物形成以防止再复制。在 G1 期，双联蛋白水平由后期促进复合物/环体 (APC/C) 泛素连接酶复合物控制，该复合物以双联蛋白为目标进行蛋白酶体降解，以形成复制前复合物。相反，从S到G2，geminin由于APC/C泛素连接酶复合物的抑制而稳定，确保了复制前复合物形成的抑制。然而，迄今为止尚未描述双联蛋白的有丝分裂调节。在这里，我们表明 Aurora-A 在 M 期期间磷酸化 Thr25 上的双联蛋白，并且该事件通过防止有丝分裂期间 APC/C 泛素连接酶复合物介导的降解来诱导双联蛋白稳定。反过来，稳定的geminin 会抑制SCFSkp2 介导的Cdt1 降解，以确保随后的S 期中复制前复合物的形成。因此，Aurora-A-geminin-Cdt1 轴代表了正确 DNA 复制的关键调节因子。 Geminin 阻止复制前复合物在 DNA 上的不当组装，并且这种活性在 G1 中通过其蛋白酶体降解而受到抑制。恒松等人。证明 Geminin 在有丝分裂过程中由于其被有丝分裂激酶 Aurora-A 磷酸化而稳定。
Geminin, an essential factor for DNA replication, directly binds to the licensing factor Cdt1 and inhibits pre-replicative complex formation to prevent re-replication. In G1, geminin levels are controlled by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex, which targets geminin for proteasomal degradation to allow pre-replicative complex formation. Conversely, from S to G2, geminin is stabilized due to APC/C ubiquitin ligase complex inhibition, ensuring the inhibition of pre-replicative complex formation. However, mitotic regulation of geminin has hitherto not been described. Here we show that Aurora-A phosphorylates geminin on Thr25 during M phase, and this event induces geminin stabilization by preventing its APC/C ubiquitin ligase complex-mediated degradation during mitosis. In turn, stabilized geminin inhibits SCFSkp2-mediated degradation of Cdt1 to ensure pre-replicative complex formation in the ensuing S phase. The Aurora-A–geminin–Cdt1 axis therefore represents a critical regulator of proper DNA replication. Geminin blocks the inappropriate assembly of pre-replication complexes on DNA, and this activity is inhibited in G1 by its proteasomal degradation. Tsunematsu et al. demonstrate that geminin is stabilized during mitosis due to its phosphorylation by the mitotic kinase Aurora-A.
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影响因子：
64.5
作者：
Bassermann, Florian;Frescas, David;Guardavaccaro, Daniele;Busino, Luca;Peschiaroli, Angelo;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
11.4
作者：
Lutzmann, Malik;Maiorano, Domenico;Mechali, Marcel
通讯作者：
Mechali, Marcel
DOI：
10.1083/jcb.200403106
发表时间：
2004-05-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Melixetian M;Ballabeni A;Masiero L;Gasparini P;Zamponi R;Bartek J;Lukas J;Helin K
通讯作者：
Helin K
影响因子：
11.4
作者：
Ballabeni, A;Melixetian, M;Helin, K
通讯作者：
Helin, K
影响因子：
21.3
作者：
Li, A;Blow, JJ
通讯作者：
Blow, JJ