Genome-wide analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine at single-nucleotide resolution unveils reduced occurrence of oxidative damage at G-quadruplex sites.

Genome-wide analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine at single-nucleotide resolution unveils reduced occurrence of oxidative damage at G-quadruplex sites.
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在单核苷酸分辨率下对8-氧代-7,8-二氢-2 '-脱氧鸟苷的全基因组分析揭示了G-四链体位点处氧化损伤的发生率降低。

DOI:
10.1093/nar/gkab1022
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发表时间:
2021-12-02
影响因子:
14.9
通讯作者:
Hu J
Hu J
中科院分区:
生物学2区
文献类型:
--
作者:
An J;Yin M;Yin J;Wu S;Selby CP;Yang Y;Sancar A;Xu GL;Qian M;Hu J

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8-氧代-7,8-二氢-2 ′-脱氧鸟苷(OG)是最常见的DNA氧化损伤之一,可引起基因组不稳定,与癌症、神经系统疾病和衰老有关。此外,OG及其修复中间体可以调节基因转录,从而在感受细胞氧化应激中发挥作用。然而,缺乏精确定位OG的方法阻碍了对其生物学作用的研究。在这里,我们开发了一种单核苷酸分辨率OG测序方法,命名为CLAPS-seq(化学标记和聚合酶停止测序),以测量外源性和内源性OG的全基因组分布,具有高度特异性。我们的数据确定了减少OG发生在G-四链体(G4),在具有高GC含量的启动子中的OG的代表性不足。此外,我们发现潜在的四链体序列(PQS)是OGs的热点,这意味着非G4-PQS在OGs介导的氧化应激反应中的作用。
8-Oxo-7,8-dihydro-2′-deoxyguanosine (OG), one of the most common oxidative DNA damages, causes genome instability and is associated with cancer, neurological diseases and aging. In addition, OG and its repair intermediates can regulate gene transcription, and thus play a role in sensing cellular oxidative stress. However, the lack of methods to precisely map OG has hindered the study of its biological roles. Here, we developed a single-nucleotide resolution OG-sequencing method, named CLAPS-seq (Chemical Labeling And Polymerase Stalling Sequencing), to measure the genome-wide distribution of both exogenous and endogenous OGs with high specificity. Our data identified decreased OG occurrence at G-quadruplexes (G4s), in association with underrepresentation of OGs in promoters which have high GC content. Furthermore, we discovered that potential quadruplex sequences (PQSs) were hotspots of OGs, implying a role of non-G4-PQSs in OG-mediated oxidative stress response.
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