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- Title
High-resolution analysis for urinary DNA jagged ends.
- Authors
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
- Abstract
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.
- Subjects
DOUBLE-strand DNA breaks; CYTOSINE; HEPARIN; CHROMATIN; RENAL cell carcinoma
- Publication
NPJ Genomic Medicine, 2022, Vol 7, Issue 1, p1
- ISSN
2056-7944
- Publication type
Article
- DOI
10.1038/s41525-022-00285-1