Nascent transcription of MCM2-7 is important for nuclear localization of the minichromosome maintenance complex in G1
Nascent transcription of MCM2-7 is important for nuclear localization of the minichromosome maintenance complex in G1
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DOI：
10.1091/mbc.e06-09-0792
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发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Breeden, Linda L.
中科院分区：
文献类型：
--
作者：
Braun, Katherine A.;Breeden, Linda L.
微小染色体维持基因(MCM2-7)在M/G(1)转录，就像MCM复合体被输入到细胞核中组装成复制前复合体一样，在细胞周期蛋白依赖性激酶(CDK)活性较低的时期。在S期，CDK通过从细胞核输出McM2-7来触发DNA复制并阻止再复制。我们发现，单个细胞周期中MCM2-7转录的抑制干扰了随后M/G(1)期的MCM的核输入。这表明新生的MCM蛋白优先被输入到细胞核中。与此一致，我们发现G(2)/M中CDK活性的丧失不足以满足核进口，还需要新的蛋白质合成。Cdc6的结构性生产不能满足这一要求，也不涉及合成新的运输机械。在前一个细胞周期中产生的MCM蛋白不能在细胞核中重新积聚，在有丝分裂晚期/G(1)早期，主要被泛素介导的蛋白分解所翻转。因此，McM2-7的核定位依赖于McM2-7的新转录和翻译，以及随着细胞进入G(1)而同时发生的CDK活性的消除。
The minichromosome maintenance genes (MCM2-7) are transcribed at M/G(1) just as the Mcm complex is imported into the nucleus to be assembled into prereplication complexes, during a period of low cyclin-dependent kinase (CDK) activity. The CDKs trigger DNA replication and prevent rereplication in part by exporting Mcm2-7 from the nucleus during S phase. We have found that repression of MCM2-7 transcription in a single cell cycle interferes with the nuclear import of Mcms in the subsequent M/G(1) phase. This suggests that nascent Mcm proteins are preferentially imported into the nucleus. Consistent with this, we find that loss of CDK activity in G(2)/M is not sufficient for nuclear import, there is also a requirement for new protein synthesis. This requirement is not met by constitutive production of Cdc6 and does not involve synthesis of new transport machinery. The Mcm proteins generated in the previous cell cycle, which are unable to reaccumulate in the nucleus, are predominantly turned over by ubiquitin-mediated proteolysis in late mitosis/early G(1) Therefore, the nuclear localization of Mcm2-7 is dependent on nascent transcription and translation of Mcm2-7 and the elimination of CDK activity which occurs simultaneously as cells enter G(1).