Dynamic maps of UV damage formation and repair for the human genome
Dynamic maps of UV damage formation and repair for the human genome
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DOI：
10.1073/pnas.1706522114
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发表时间：
2017-06-27
影响因子：
11.1
通讯作者：
Sancar, Aziz
中科院分区：
文献类型：
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作者：
Hu, Jinchuan;Adebali, Ogun;Sancar, Aziz
紫外线诱导的人类细胞DNA损伤的形成和修复受到细胞环境的影响。为了研究影响损伤形成和修复全基因组的因素，我们开发了一种高灵敏度的单核苷酸分辨率损伤定位方法[高灵敏度损伤测序（HS-Damage-seq）]。来自UV照射的细胞和裸DNA的环丁烷嘧啶二聚体（CPD）和嘧啶-嘧啶酮（6-4）光产物[（6 -4）PP]的损伤图谱显示，转录因子结合对大体积加合物形成的影响各不相同，取决于特定的转录因子、损伤类型和链。我们还通过HS-Damage-seq生成了CPD和（6-4）PP的时间分辨UV损伤图，并将其与通过切除修复测序获得的人类基因组的互补修复图进行比较，以深入了解影响UV诱导的DNA损伤和修复以及最终UV致癌作用的因素。这两种方法的结合表明，虽然紫外线诱导的损伤在整个基因组中几乎是均匀的，但修复受染色质状态、转录和转录因子结合的影响，其方式取决于DNA损伤的类型。
Formation and repair of UV-induced DNA damage in human cells are affected by cellular context. To study factors influencing damage formation and repair genome-wide, we developed a highly sensitive single-nucleotide resolution damage mapping method [high-sensitivity damage sequencing (HS-Damage-seq)]. Damage maps of both cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts [(6-4) PPs] from UV-irradiated cellular and naked DNA revealed that the effect of transcription factor binding on bulky adducts formation varies, depending on the specific transcription factor, damage type, and strand. We also generated time-resolved UV damage maps of both CPDs and (6-4) PPs by HS-Damage-seq and compared them to the complementary repair maps of the human genome obtained by excision repair sequencing to gain insight into factors that affect UV-induced DNA damage and repair and ultimately UV carcinogenesis. The combination of the two methods revealed that, whereas UV-induced damage is virtually uniform throughout the genome, repair is affected by chromatin states, transcription, and transcription factor binding, in a manner that depends on the type of DNA damage.