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组蛋白 mRNA 代谢和 DNA 复制的协调调控:细胞周期蛋白 A/CDK1 参与 S 期结束时组蛋白 mRNA 代谢和 DNA 复制的失活。

Coordinate regulation of histone mRNA metabolism and DNA replication: cyclin A/cdk1 is involved in inactivation of histone mRNA metabolism and DNA replication at the end of S phase.

机构信息

Department of Biology and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Cell Cycle. 2010 Oct 1;9(19):3857-63. doi: 10.4161/cc.9.19.13300. Epub 2010 Oct 9.

DOI:10.4161/cc.9.19.13300
PMID:20935461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3047749/
Abstract

S phase is characterized by the replication of DNA and assembly of chromatin. This requires the synthesis of large amounts of histone proteins to package the newly replicated DNA. Histone mRNAs are the only mRNAs that do not have polyA tails, ending instead in a conserved stemloop sequence. The stemloop binding protein (SLBP) that binds the 3' end of histone mRNA is cell cycle regulated and SLBP is required in all steps of histone mRNA metabolism. Activation of cyclin E/cdk2 prior to entry into S-phase is critical for initiation of DNA replication and histone mRNA accumulation. At the end of S phase SLBP is rapidly degraded as a result of phosphorylation of SLBP by cyclin A/cdk1 and CK2 effectively shutting off histone mRNA biosynthesis. E2F1, which is required for expression of many S-phase genes, is regulated in parallel with SLBP and its degradation also requires a cyclin binding site, suggesting that it may also be regulated by the same pathway. It is likely that activation of cyclin A/cdk1 helps inhibit both DNA replication and histone mRNA accumulation, marking the end of S phase and entry into G(2)-phase.

摘要

S 期的特征是 DNA 的复制和染色质的组装。这需要合成大量的组蛋白蛋白质来包装新复制的 DNA。组蛋白 mRNA 是唯一没有 polyA 尾巴的 mRNA,而是以保守的茎环序列结尾。与组蛋白 mRNA 3' 端结合的茎环结合蛋白 (SLBP) 受细胞周期调控,并且在组蛋白 mRNA 代谢的所有步骤中都需要 SLBP。在进入 S 期之前,激活 cyclin E/cdk2 对于启动 DNA 复制和组蛋白 mRNA 积累至关重要。在 S 期结束时,SLBP 迅速降解,这是由于 cyclin A/cdk1 对 SLBP 的磷酸化以及 CK2 有效地关闭组蛋白 mRNA 生物合成所致。E2F1 是许多 S 期基因表达所必需的,与 SLBP 平行调控,其降解也需要一个细胞周期蛋白结合位点,表明它也可能受相同途径调控。激活 cyclin A/cdk1 可能有助于抑制 DNA 复制和组蛋白 mRNA 积累,标志着 S 期结束和 G(2)期进入。

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Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells.在人类胚胎干细胞的简化细胞周期中,组蛋白基因表达机制在亚核焦点处的阶段性组装。
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Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase.细胞周期蛋白A/细胞周期蛋白依赖性激酶1对苏氨酸61的磷酸化作用会在S期结束时引发茎环结合蛋白的降解。
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