Protein kinase A is required for chromosomal DNA replication
Protein kinase A is required for chromosomal DNA replication
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DOI：
10.1016/s0960-9822(99)80395-9
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发表时间：
1999-08-26
期刊：
影响因子：
9.2
通讯作者：
Grieco, D
中科院分区：
文献类型：
--
作者：
Costanzo, V;Avvedimento, EV;Grieco, D
通过有丝分裂重置细胞进行新一轮的染色体DNA复制[1]，在有丝分裂晚期，复制前复合物-包括起点识别复合物（ORC），Cdc 6和微型染色体维持（MCM）蛋白-结合染色质作为DNA复制的先决条件。然后，S期促进细胞周期蛋白依赖性激酶（Cdks）和激酶Dbf 4-Cdc 7起作用以启动复制。在复制开始之前，Cdc 6从染色质解离。S期和M期Cdks阻断新的复制前复合物的形成，防止细胞周期的S、G2和M期期间的DNA过度复制[1]。核膜也有助于将基因组复制限制在每个细胞周期一次[2]，因此，在M期结束时，核膜破裂和Cdk活性的崩溃重置细胞进行新一轮的染色体复制。我们以前发现，蛋白激酶A（PKA）活性振荡在非洲爪蟾卵提取物的细胞周期中，在有丝分裂晚期达到峰值，振荡是由M期促进Cdk诱导的[3，4]，在这里，我们发现PKA振荡是DNA复制的下一阶段所必需的。PKA活性从有丝分裂的退出到核膜的形成是必需的。ORC 2、Cdc 6和MCM 3在染色质上的组装不需要PKA。抑制PKA活性，但是，阻止Cdc 6从染色质和随后的DNA复制的释放。这些数据表明，PKA激活在M期后期是需要为后续的S期。
Passage through mitosis resets cells for a new round of chromosomal DNA replication [1], In late mitosis, the pre-replication complex - which includes the origin recognition complex (ORC), Cdc6 and the minichromosome maintenance (MCM) proteins - binds chromatin as a pre-requisite for DNA replication. S-phase promoting cyclin-dependent kinases (Cdks) and the kinase Dbf4-Cdc7 then act to initiate replication. Before the onset of replication Cdc6 dissociates from chromatin. S-phase and M-phase Cdks block the formation of a new pre-replication complex, preventing DNA over-replication during the S, G2 and M phases of the cell cycle [1]. The nuclear membrane also contributes to limit genome replication to once per cell cycle [2], Thus, at the end of M phase, nuclear membrane breakdown and the collapse of Cdk activity reset cells for a new round of chromosomal replication. We showed previously that protein kinase A (PKA) activity oscillates during the cell cycle in Xenopus egg extracts, peaking in late mitosis, The oscillations are induced by the M-phase-promoting Cdk [3,4], Here, we found that PKA oscillation was required for the following phase of DNA replication. PKA activity was needed from mitosis exit to the formation of the nuclear envelope. PKA was not required for the assembly of ORC2, Cdc6 and MCM3 onto chromatin. Inhibition of PKA activity, however, blocked the release of Cdc6 from chromatin and subsequent DNA replication. These data suggest that PKA activation in late M phase is required for the following S phase.