Super hotspots and super coldspots in the repair of UV-induced DNA damage in the human genome.
Super hotspots and super coldspots in the repair of UV-induced DNA damage in the human genome.
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DOI：
10.1016/j.jbc.2021.100581
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Sancar A
中科院分区：
文献类型：
--
作者：
Jiang Y;Li W;Lindsey-Boltz LA;Yang Y;Li Y;Sancar A
紫外线诱导的DNA损伤的形成及其修复受到许多调节损伤形成和修复机制可及性的因素的影响。然而，仍然不知道哪些基因组位点优先用于UV损伤诱导后的立即修复，以及这些优先位点是否与UV损伤的热点重叠。我们通过使用eXcision修复测序（XR-seq）方法鉴定了（6-4）嘧啶-嘧啶酮光产物最早修复的超级热点。我们通过分析可用的XR-seq时程数据进一步鉴定了（6-4）嘧啶-嘧啶酮光产物修复的超级冷点和环丁烷嘧啶二聚体修复的超级热点。通过整合XR-seq，Damage-seq，adductSeq和环丁烷嘧啶二聚体-seq的数据集，我们表明修复超级热点和修复超级冷点都不会与UV损伤的热点重叠。此外，我们证明了修复超级热点显着丰富的频繁相互作用的区域和superenhancers。最后，我们报告了我们的发现，丰富的胞嘧啶修复超级热点和超级冷点。这些研究结果表明，本地DNA功能连同大规模的染色质功能有助于数量级的变化率的紫外线损伤修复。
The formation of UV-induced DNA damage and its repair are influenced by many factors that modulate lesion formation and the accessibility of repair machinery. However, it remains unknown which genomic sites are prioritized for immediate repair after UV damage induction, and whether these prioritized sites overlap with hotspots of UV damage. We identified the super hotspots subject to the earliest repair for (6-4) pyrimidine–pyrimidone photoproduct by using the eXcision Repair-sequencing (XR-seq) method. We further identified super coldspots for (6-4) pyrimidine–pyrimidone photoproduct repair and super hotspots for cyclobutane pyrimidine dimer repair by analyzing available XR-seq time-course data. By integrating datasets of XR-seq, Damage-seq, adductSeq, and cyclobutane pyrimidine dimer-seq, we show that neither repair super hotspots nor repair super coldspots overlap hotspots of UV damage. Furthermore, we demonstrate that repair super hotspots are significantly enriched in frequently interacting regions and superenhancers. Finally, we report our discovery of an enrichment of cytosine in repair super hotspots and super coldspots. These findings suggest that local DNA features together with large-scale chromatin features contribute to the orders of magnitude variability in the rates of UV damage repair.
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影响因子：
16
作者：
Fong, Yick W.;Cattoglio, Claudia;Tjian, Robert
通讯作者：
Tjian, Robert
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
DOI：
10.1073/pnas.1603388113
发表时间：
2016-04-12
影响因子：
11.1
作者：
Adar, Sheera;Hu, Jinchuan;Sancar, Aziz
通讯作者：
Sancar, Aziz
影响因子：
11.4
作者：
Garcia-Nieto, Pablo E.;Schwartz, Erin K.;Morrison, Ashby J.
通讯作者：
Morrison, Ashby J.
影响因子：
64.8
作者：
DRAPKIN, R;REARDON, JT;REINBERG, D
通讯作者：
REINBERG, D