Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin.
Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin.
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DOI：
10.1101/gr.209106.116
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发表时间：
2016-10
期刊：
影响因子：
7
通讯作者：
Reed SH
中科院分区：
文献类型：
--
作者：
Yu S;Evans K;van Eijk P;Bennett M;Webster RM;Leadbitter M;Teng Y;Waters R;Jackson SP;Reed SH
通过DNA修复去除病变的速度在整个基因组中可能有很大的差异，这对基因组的稳定性具有重要的意义。为了研究这一点，我们测量了紫外线诱导的损伤在整个萌芽酵母基因组中的核苷酸切除修复(NER)率的分布。通过绘制这些修复速率与基因及其相关侧翼序列的关系图，我们揭示了在正常细胞中，基因组修复速率显示出一种独特的模式，这表明DNA修复在基因组中是高度组织的。此外，通过比较野生型细胞和全球基因组-NER(GG-NER)亚途径缺陷细胞的全基因组DNA修复率，我们建立了这如何改变NER在整个基因组中的分布。我们还检测了紫外线照射前后GG-NER因子与染色质结合的基因组位置，发现GG-NER是从特定的基因组位置组织和启动的。在这些位点，组蛋白乙酰转移酶Gcn5的染色质占有率由GG-NER复合体控制，GG-NER复合体调节组蛋白H3乙酰化和染色质结构，从而促进紫外线诱导的损伤的有效DNA修复。因此，GG-NER过程中的染色质重塑被组织到这些基因组区域中。重要的是，Gcn5的丢失显著改变了NER率的基因组分布；这意味着染色质修饰物对整个基因组中出现的突变的分布的影响。
The rates at which lesions are removed by DNA repair can vary widely throughout the genome, with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that, in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organized within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells and cells defective in the global genome–NER (GG-NER) subpathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation, revealing that GG-NER is organized and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone acetyl-transferase Gcn5 is controlled by the GG-NER complex, which regulates histone H3 acetylation and chromatin structure, thereby promoting efficient DNA repair of UV-induced lesions. Chromatin remodeling during the GG-NER process is therefore organized into these genomic domains. Importantly, loss of Gcn5 significantly alters the genomic distribution of NER rates; this has implications for the effects of chromatin modifiers on the distribution of mutations that arise throughout the genome.
影响因子：
3.7
作者：
Zhang X;Yu Q;Olsen L;Bi X
通讯作者：
Bi X