Paving the way for H2AX phosphorylation Chromatin changes in the DNA damage response
Paving the way for H2AX phosphorylation Chromatin changes in the DNA damage response
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DOI：
10.4161/cc.8.10.8501
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发表时间：
2009-05-15
期刊：
影响因子：
4.3
通讯作者：
Venkitaraman, Ashok R.
中科院分区：
文献类型：
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作者：
Ayoub, Nabieh;Jeyasekharan, Anand D.;Venkitaraman, Ashok R.
染色质相关蛋白的动力学控制着DNA对转录、复制、重组和修复等基本生物学事务的可及性。在这里，我们简要概述了什么是已知的细胞响应DNA断裂过程中发生的染色质变化，集中在我们最近的研究结果揭示，染色质因子HP1 β在DNA损伤后几秒钟内动员酪蛋白激酶2（CK2）磷酸化介导的未识别的信号级联，为组蛋白H2AX磷酸化铺平了道路。我们还表明，HP 1 β动员既不与组蛋白H3修饰Ser10，改变建议，以协助HP 1喷射染色质，也没有证据表明HP 1 β和CK2调节亚基之间的物理相互作用。有趣的是，在其快速动员后，我们发现HP1 β在较长的时间内逐渐在受损的染色质上重新积累，这表明HP1 β动力学的时间变化和与染色质的相互作用可能有助于细胞对DNA断裂反应的不同阶段。
The dynamics of chromatin-associated proteins control the accessibility of DNA to essential biological transactions like transcription, replication, recombination and repair. Here, we briefly outline what is known about the chromatin changes that occur during the cellular response to DNA breakage, focusing on our recent findings revealing that the chromatin factor HP1 beta is mobilized within seconds after DNA damage by an unrecognized signaling cascade mediated by casein kinase 2 (CK2) phosphorylation, paving the way for histone H2AX phosphorylation. We also show here that HP1 beta mobilization is neither associated with histone H3 modification on Ser10, an alteration proposed to assist in HP1 ejection from chromatin, nor with evidence of a physical interaction between HP1 beta and the CK2 regulatory subunit. Interestingly, following its rapid mobilization, we find that HP1 beta gradually re-accumulates on damaged chromatin over a longer time period, suggesting that temporal changes in HP1 beta dynamics and interaction with chromatin may assist in different stages of the cellular response to DNA breakage.