Nucleosome remodeling at origins of global genome-nucleotide excision repair occurs at the boundaries of higher-order chromatin structure.
Nucleosome remodeling at origins of global genome-nucleotide excision repair occurs at the boundaries of higher-order chromatin structure.
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全球基因组核苷酸切除修复起源的核小体重塑发生在高级染色质结构的边界处。
DOI：
10.1101/gr.237198.118
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发表时间：
2019
期刊：
影响因子：
7
通讯作者：
Van Eijk P
中科院分区：
文献类型：
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作者：
Van Eijk P
UV诱导的DNA损伤的修复需要染色质重塑。修复是如何在染色质中启动的仍然是未知的。我们最近证明，全球基因组核苷酸切除修复（GG-NER）在染色质中的组织结构域有关的开放阅读框架。在这里，我们定义这些域，确定修复启动的基因组位置。通过研究DNA损伤诱导的变化，在这些网站的核小体的线性结构，我们展示了如何染色质重塑启动GG-NER。在未受损的细胞中，我们发现GG-NER复合物占据染色质，在这些基因组位置建立核小体结构，我们称之为GG-NER复合物结合位点（GCBSs）。我们证明，这些网站经常位于基因组边界描绘染色体相互作用域（CID）。这些边界定义了高阶核小体-核小体相互作用的域。我们证明，启动GG-NER在染色质中是伴随着中断的动态核小体侧翼GCBSs的GG-NER复合物。
Repair of UV-induced DNA damage requires chromatin remodeling. How repair is initiated in chromatin remains largely unknown. We recently demonstrated that global genome–nucleotide excision repair (GG-NER) in chromatin is organized into domains in relation to open reading frames. Here, we define these domains, identifying the genomic locations from which repair is initiated. By examining DNA damage–induced changes in the linear structure of nucleosomes at these sites, we demonstrate how chromatin remodeling is initiated during GG-NER. In undamaged cells, we show that the GG-NER complex occupies chromatin, establishing the nucleosome structure at these genomic locations, which we refer to as GG-NER complex binding sites (GCBSs). We demonstrate that these sites are frequently located at genomic boundaries that delineate chromosomally interacting domains (CIDs). These boundaries define domains of higher-order nucleosome–nucleosome interaction. We demonstrate that initiation of GG-NER in chromatin is accompanied by the disruption of dynamic nucleosomes that flank GCBSs by the GG-NER complex.