Protein kinase C coordinates histone H3 phosphorylation and acetylation.
Protein kinase C coordinates histone H3 phosphorylation and acetylation.
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DOI：
10.7554/elife.09886
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发表时间：
2015-10-15
期刊：
影响因子：
7.7
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Darieva Z;Webber A;Warwood S;Sharrocks AD
DNA复制后染色质的重新组装是维持基因组完整性的关键事件。组蛋白H3在K56处的乙酰化和在T45处的磷酸化是伴随染色质组装的两个重要的染色质修饰。在这里，我们已经确定了蛋白激酶Pkc1作为一个关键的调节器，协调这些修饰在S。在复制应激条件下的酿酒酵母。Pkc1磷酸化组蛋白乙酰转移酶Rtt109并促进其乙酰化H3K56的能力。我们的数据还揭示了两种不同的组蛋白修饰之间的新的串扰，因为Pkc1也增强了H3T45磷酸化，并且这种修饰是H3K56乙酰化所必需的。因此，我们的数据揭示了一个重要的作用，Pkc1在协调沉积的两个不同的组蛋白修饰是重要的染色质组装。http://dx.doi.org/10.7554/eLife.09886.001在细胞分裂之前，DNA必须被复制，以便每个新细胞都能获得细胞遗传指令的完整副本。但是DNA是如此之长，以至于它以高度压缩的形式储存在细胞核中，DNA链盘绕在几种称为组蛋白的蛋白质周围。在复制DNA之前，它必须展开。然后，每一个新的DNA拷贝必须重新包装，以适应每个新细胞的细胞核内的复杂性。如果在复制DNA的过程中发生错误，可能会导致基因突变，从而导致癌症等疾病。为了防止这种情况，细胞有机制来识别错误并在DNA重新包装之前纠正它们。这需要暂停，以便在DNA反冲之前进行修复。然而，目前还不完全清楚这一过程是如何控制的。现在，Darieva等人表明，一种称为蛋白激酶C（或简称Pkc1）的酶在错误被纠正后对重新包装DNA至关重要。一些实验表明，当细胞暴露于可能导致DNA复制错误的应激条件时，Pkc1起着重要作用。具体来说，Pkc1帮助准备第三组蛋白（组蛋白H3），这样DNA就可以在它周围弹回。Pkc1等待，直到压力条件过去，DNA已经修复，以进行必要的改变。一旦压力过去，Pkc1就会向另一种称为Rtt109的酶添加磷酸盐，以制备组蛋白。Pkc1同时也促进了组蛋白H3的另一个必要变化。这些关于DNA重新包装的新细节可能有助于研究人员了解细胞如何防止DNA复制错误，以及这个过程在癌症中是如何出错的。DOI：http://dx.doi.org/10.7554/eLife.09886.002网站
The re-assembly of chromatin following DNA replication is a critical event in the maintenance of genome integrity. Histone H3 acetylation at K56 and phosphorylation at T45 are two important chromatin modifications that accompany chromatin assembly. Here we have identified the protein kinase Pkc1 as a key regulator that coordinates the deposition of these modifications in S. cerevisiae under conditions of replicative stress. Pkc1 phosphorylates the histone acetyl transferase Rtt109 and promotes its ability to acetylate H3K56. Our data also reveal novel cross-talk between two different histone modifications as Pkc1 also enhances H3T45 phosphorylation and this modification is required for H3K56 acetylation. Our data therefore uncover an important role for Pkc1 in coordinating the deposition of two different histone modifications that are important for chromatin assembly. DOI: http://dx.doi.org/10.7554/eLife.09886.001 Prior to cell division, DNA must be copied so that each new cell gets a complete copy of the cell’s genetic instructions. But DNA is so long that it is stored in a heavily compacted form in the nucleus of the cell, with the strands of DNA coiled around several proteins called histones. Before the DNA is copied, it must be unfurled. Then each new copy of DNA must be repackaged to fit compactly inside the nucleus of each new cell. If errors occur in the process of copying DNA, it can lead to genetic mutations that may cause diseases like cancer. To prevent this, cells have mechanisms to identify errors and correct them before the DNA is repackaged. This requires a pause to allow the repairs to occur before the DNA recoils. However, it is not completely clear how this process is controlled. Now, Darieva et al. show that an enzyme called protein kinase C (or Pkc1 for short) is essential to repackaging DNA after the errors are corrected. Several experiments showed that Pkc1 plays an important role when cells were exposed to stressful conditions that potentially cause errors in DNA copying. Specifically, Pkc1 helps prepare the third histone protein (histone H3) so that DNA can recoil around it. Pkc1 waits until the stressful conditions have passed and the DNA has been repaired to make the necessary changes. Once the stress has passed, Pkc1 adds a phosphate to another enzyme called Rtt109 that prepares the histone. The Pkc1 simultaneously contributes to another necessary change to histone H3. These new details about DNA repackaging may help researchers understand how cells protect against DNA copying errors, and how this process goes wrong in cancer. DOI: http://dx.doi.org/10.7554/eLife.09886.002