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

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
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DOI：
10.4161/cc.9.19.13300
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发表时间：
2010-10-01
期刊：
CELL CYCLE
影响因子：
4.3
通讯作者：
Marzluff, William F.
Marzluff, William F.
中科院分区：
生物学3区
文献类型：
--
作者：
Koseoglu, M. Murat;Dong, Jian;Marzluff, William F.

文献摘要

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S期的特点是DNA复制和染色质组装。这需要合成大量的组蛋白来包装新复制的DNA。组蛋白 mRNA 是唯一没有多聚腺苷酸尾巴的 mRNA，而是以保守的茎环序列结尾。结合组蛋白 mRNA 3' 端的茎环结合蛋白 (SLBP) 受细胞周期调节，组蛋白 mRNA 代谢的所有步骤都需要 SLBP。进入 S 期之前，细胞周期蛋白 E/cdk2 的激活对于 DNA 复制的启动和组蛋白 mRNA 的积累至关重要。在 S 期末，由于细胞周期蛋白 A/cdk1 和 CK2 磷酸化 SLBP，SLBP 迅速降解，有效关闭组蛋白 mRNA 生物合成。 E2F1 是许多 S 期基因表达所必需的，与 SLBP 并行调节，其降解也需要细胞周期蛋白结合位点，表明它也可能受到相同途径的调节。 cyclin A/cdk1 的激活可能有助于抑制 DNA 复制和组蛋白 mRNA 积累，标志着 S 期的结束并进入 G(2) 期。
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.