尿DNA锯齿状末端的高分辨率分析。
High-resolution analysis for urinary DNA jagged ends.
作者信息
Xie Tingting, Wang Guangya, Ding Spencer C, Lee Wing-Shan, Cheng Suk Hang, Chan Rebecca W Y, Zhou Ze, Ma Mary-Jane L, Han Diana S C, Teoh Jeremy Y C, Lam W K Jacky, Jiang Peiyong, Chiu Rossa W K, Chan K C Allen, Lo Y M Dennis
机构信息
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
出版信息
NPJ Genom Med. 2022 Feb 23;7(1):14. doi: 10.1038/s41525-022-00285-1.
Single-stranded ends of double-stranded DNA (jagged ends) are more abundant in urinary DNA than in plasma DNA. However, the lengths of jagged ends in urinary DNA remained undetermined, as a previous method used for urinary DNA jagged end sequencing analysis (Jag-seq) relied on unmethylation at CpG sites, limiting the resolution. Here, we performed high-resolution Jag-seq analysis using methylation at non-CpG cytosine sites, allowing determination of exact length of jagged ends. The urinary DNA bore longer jagged ends (26-nt) than plasma DNA (17-nt). The jagged end length distribution displayed 10-nt periodicities in urinary DNA, which were much less observable in plasma DNA. Amplitude of the 10-nt periodicities increased in patients with renal cell carcinoma. Heparin treatment of urine diminished the 10-nt periodicities. The urinary DNA jagged ends often extended into nucleosomal cores, suggesting potential interactions with histones. This study has thus advanced our knowledge of jagged ends in urine DNA.
双链DNA的单链末端（锯齿状末端）在尿液DNA中比在血浆DNA中更为丰富。然而，尿液DNA中锯齿状末端的长度仍未确定，因为先前用于尿液DNA锯齿状末端测序分析（Jag-seq）的方法依赖于CpG位点的未甲基化，限制了分辨率。在此，我们使用非CpG胞嘧啶位点的甲基化进行了高分辨率Jag-seq分析，从而能够确定锯齿状末端的精确长度。尿液DNA的锯齿状末端比血浆DNA的更长（约26个核苷酸）（约17个核苷酸）。锯齿状末端长度分布在尿液DNA中呈现10个核苷酸的周期性，而在血浆DNA中则不太明显。肾细胞癌患者中10个核苷酸周期性的幅度增加。尿液的肝素处理减少了10个核苷酸的周期性。尿液DNA锯齿状末端常常延伸到核小体核心，表明其与组蛋白存在潜在相互作用。因此，本研究增进了我们对尿液DNA中锯齿状末端的了解。
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