Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2.
Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2.
复制标题
鉴定DNA复制中的预启动步骤，该步骤独立于原点识别复合物和CDC6，但取决于CDK2。
DOI：
10.1083/jcb.140.2.271
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发表时间：
1998-01-26
影响因子：
7.8
通讯作者：
Newport, J
中科院分区：
文献类型：
--
作者：
Hua, XQH;Newport, J
在DNA复制开始之前，起始点识别复合物（ORC）蛋白、cdc6和微小染色体维持（MCM）蛋白依次与染色质结合并形成预起始复合物。使用非洲爪蟾卵提取物，我们发现，这些复合物的形成和DNA复制开始之前，cdc6迅速从染色质中去除，可能是由cdk2激活的，泛素依赖的蛋白水解途径降解。如果这种置换被抑制，DNA复制就不能启动。我们还发现，MCM蛋白组装成preinitiation复合物后，从DNA中去除ORC不会阻止随后的复制起始。重要的是，在ORC和cdc6蛋白都不存在于前起始复合物的条件下，DNA复制仍然依赖于cdk2活性。因此，导致在细胞周期的S期期间启动DNA复制的过程中的最后步骤不依赖于ORC和cdc6蛋白，而是依赖于cdk2活性。
Before initiation of DNA replication, origin recognition complex (ORC) proteins, cdc6, and minichromosome maintenance (MCM) proteins bind to chromatin sequentially and form preinitiation complexes. Using Xenopus laevis egg extracts, we find that after the formation of these complexes and before initiation of DNA replication, cdc6 is rapidly removed from chromatin, possibly degraded by a cdk2-activated, ubiquitin-dependent proteolytic pathway. If this displacement is inhibited, DNA replication fails to initiate. We also find that after assembly of MCM proteins into preinitiation complexes, removal of the ORC from DNA does not block the subsequent initiation of replication. Importantly, under conditions in which both ORC and cdc6 protein are absent from preinitiation complexes, DNA replication is still dependent on cdk2 activity. Therefore, the final steps in the process leading to initiation of DNA replication during S phase of the cell cycle are independent of ORC and cdc6 proteins, but dependent on cdk2 activity.
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影响因子：
10.5
作者：
Jallepalli, PV;Kelly, TJ
通讯作者：
Kelly, TJ
影响因子：
11.4
作者：
Coue, M;Kearsey, SE;Mechali, M
通讯作者：
Mechali, M
影响因子：
64.8
作者：
BROEK, D;BARTLETT, R;NURSE, P
通讯作者：
NURSE, P
影响因子：
64.5
作者：
CORREABORDES, J;NURSE, P
通讯作者：
NURSE, P
影响因子：
9.2
作者：
DAHMANN, C;DIFFLEY, JFX;NASMYTH, KA
通讯作者：
NASMYTH, KA