High-resolution analysis for urinary DNA jagged ends

• Published in: Npj genomic medicine Vol. 7; no. 1; p. 14
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-02-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/61/514/1948; 631/67/1857; Bioinformatics; Biomedical and Life Sciences; Biomedicine; CpG islands; Cytosine; DNA methylation; DNA sequencing; Gene Function; Gene Therapy; Heparin; Histones; Human Genetics; Internal Medicine; Kidney cancer; Renal cell carcinoma; Sequence analysis; Single-stranded DNA
• ISSN: 2056-7944; 2056-7944
• 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.