High-resolution analysis for urinary DNA jagged ends

Tingting Xie; Guangya Wang; Spencer C. Ding; Wing Shan Lee; Suk Hang Cheng; Rebecca W.Y. Chan; Ze Zhou; Mary Jane L. Ma; Diana S.C. Han; Jeremy Y.C. Teoh; W. K. Jacky Lam; Peiyong Jiang; Rossa W.K. Chiu; K. C.Allen Chan; Y. M.Dennis Lo

doi:10.1038/s41525-022-00285-1

High-resolution analysis for urinary DNA jagged ends

Tingting Xie, Guangya Wang, Spencer C. Ding, Wing Shan Lee, Suk Hang Cheng, Rebecca W.Y. Chan, Ze Zhou, Mary Jane L. Ma, Diana S.C. Han, Jeremy Y.C. Teoh, W. K. Jacky Lam, Peiyong Jiang, Rossa W.K. Chiu, K. C.Allen Chan, Y. M.Dennis Lo^*

^*Corresponding author for this work

Department of Physics

Research output: Contribution to journal › Journal article › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	14
Number of pages	8
Journal	npj Genomic Medicine
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41525-022-00285-1
Publication status	Published - 23 Feb 2022

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title = "High-resolution analysis for urinary DNA jagged ends",

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.",

author = "Tingting Xie and Guangya Wang and Ding, {Spencer C.} and Lee, {Wing Shan} and Cheng, {Suk Hang} and Chan, {Rebecca W.Y.} and Ze Zhou and Ma, {Mary Jane L.} and Han, {Diana S.C.} and Teoh, {Jeremy Y.C.} and Lam, {W. K. Jacky} and Peiyong Jiang and Chiu, {Rossa W.K.} and Chan, {K. C.Allen} and Lo, {Y. M.Dennis}",

note = "This work was supported by the Research Grants Council of the Hong Kong SAR Government under the Theme-based Research Scheme (T12-401/16-W), a collaborative research agreement from Grail, the Innovation and Technology Commission, and the Vice Chancellor{\textquoteright}s One-Off Discretionary Fund of The Chinese University of Hong Kong (VCF2014021). Y.M.D.L. is supported by an endowed chair from the Li Ka Shing Foundation. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Xie, Tingting

AU - Wang, Guangya

AU - Ding, Spencer C.

AU - Lee, Wing Shan

AU - Cheng, Suk Hang

AU - Chan, Rebecca W.Y.

AU - Zhou, Ze

AU - Ma, Mary Jane L.

AU - Han, Diana S.C.

AU - Teoh, Jeremy Y.C.

AU - Lam, W. K. Jacky

AU - Jiang, Peiyong

AU - Chiu, Rossa W.K.

AU - Chan, K. C.Allen

AU - Lo, Y. M.Dennis

N1 - This work was supported by the Research Grants Council of the Hong Kong SAR Government under the Theme-based Research Scheme (T12-401/16-W), a collaborative research agreement from Grail, the Innovation and Technology Commission, and the Vice Chancellor’s One-Off Discretionary Fund of The Chinese University of Hong Kong (VCF2014021). Y.M.D.L. is supported by an endowed chair from the Li Ka Shing Foundation. Publisher Copyright: © 2022, The Author(s).

PY - 2022/2/23

Y1 - 2022/2/23

N2 - 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.

AB - 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.

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High-resolution analysis for urinary DNA jagged ends

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