ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor
ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor
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DOI：
10.1128/mcb.20.20.7643-7653.2000
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发表时间：
2000-10-01
影响因子：
5.3
通讯作者：
Vermeulen, W
中科院分区：
文献类型：
--
作者：
Citterio, E;Van Den Boom, V;Vermeulen, W
Cockayne综合征B蛋白（CS B）是在称为转录偶联修复（TCR）的过程中将DNA切除修复偶联至转录所必需的。Cockayne综合征患者表现出紫外线敏感性和严重的神经发育异常。CSB是SW 12/SNF 2家族的DNA依赖性ATP酶。SW 12/SNF 2样蛋白参与转录过程中的染色质重塑。由于染色质结构也影响DNA修复效率，因此预期修复中的染色质重塑活动。在这里，我们使用纯化的重组CSB蛋白，以研究它是否可以在体外重塑染色质。我们发现，CSB与DNA的结合导致DNA双螺旋构象的改变。此外，我们发现，CSB是能够重塑染色质结构的ATP水解为代价。具体地，CSB可以改变DNA酶I对重构的单核小体核心的可接近性，并打乱质粒DNA上规则间隔的核小体阵列。此外，我们表明，CSB不仅与双链DNA，但也直接与核心组蛋白相互作用。最后，完整的组蛋白尾部在CSB重塑中起重要作用。CSB是第一个发现在调节核小体结构中发挥直接作用的修复蛋白。这一发现的相关性转录和修复之间的相互作用进行了讨论。
The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB is a DNA-dependent ATPase of the SW12/SNF2 family. SW12/SNF2-like proteins are implicated in chromatin remodeling during transcription. Since chromatin structure also affects DNA repair efficiency, chromatin remodeling activities within repair are expected. Here we used purified recombinant CSB protein to investigate whether it can remodel chromatin in vitro. We show that binding of CSB to DNA results in an alteration of the DNA double-helix conformation. In addition, we find that CSB is able to remodel chromatin structure at the expense of ATP hydrolysis. Specifically, CSB can alter DNase I accessibility to reconstituted mononucleosome cores and disarrange an array of nucleosomes regularly spaced on plasmid DNA. In addition, we show that CSB interacts not only with double-stranded DNA but also directly with core histones. Finally, intact histone tails play an important role in CSB remodeling. CSB is the first repair protein found to play a direct role in modulating nucleosome structure. The relevance of this finding to the interplay between transcription and repair is discussed.