JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress.
JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress.
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DOI：
10.1016/j.molcel.2011.06.021
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发表时间：
2011-10-07
期刊：
影响因子：
16
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Miotto B;Struhl K
为了应对环境压力，细胞激活压力反应基因并抑制DNA复制。HBO 1组蛋白乙酰化酶是AP-1转录因子响应应激激活的JNK激酶的共激活因子，也是Cdt 1许可因子的共激活因子，其确保DNA在每个细胞周期精确复制一次。在非遗传毒性应激反应中，JNK磷酸化AP-1转录因子Jun，导致HBO 1募集增加和靶基因转录增加。此外，JNK磷酸化苏氨酸29上的Cdt 1，导致HBO 1从复制起点快速解离，从而阻断DNA复制的起始。在缓解压力后，HBO 1与复制起点重新关联。因此，通过JNK介导的募集转录和复制许可因子的磷酸化，HBO 1共激活因子向靶基因和复制起点的受调节和相互募集协调了对细胞应激的转录和DNA复制应答。
In response to environmental stresses, cells activate stress-response genes and inhibit DNA replication. HBO1 histone acetylase is a coactivator both for AP-1 transcription factors responding to stress-activated JNK kinases and also for the Cdt1 licensing factor that ensures that DNA is replicated exactly once per cell cycle. In response to non-genotoxic stress, JNK phosphorylates Jun, an AP-1 transcription factor, leading to increased recruitment of HBO1 and increased transcription of target genes. In addition, JNK phosphorylates Cdt1 on threonine 29, leading to rapid dissociation of HBO1 from replication origins, thereby blocking initiation of DNA replication. Upon relief of stress, HBO1 re-associates with replication origins. Thus, regulated and reciprocal recruitment of the HBO1 co-activator to target genes and replication origins via JNK-mediated phosphorylation of the recruiting transcription and replication licensing factors coordinates the transcriptional and DNA replication response to cellular stress.
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