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Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells

Author

Listed:
  • Huifen Cao

    (Huaqiao University)

  • Lorena Salazar-García

    (Huaqiao University)

  • Fan Gao

    (Huaqiao University)

  • Thor Wahlestedt

    (Huaqiao University)

  • Chun-Lin Wu

    (Second Affiliated Hospital of Fujian Medical University)

  • Xueer Han

    (Huaqiao University)

  • Ye Cai

    (Huaqiao University)

  • Dongyang Xu

    (Huaqiao University)

  • Fang Wang

    (Huaqiao University)

  • Lu Tang

    (Huaqiao University)

  • Natalie Ricciardi

    (University of Miami Miller School of Medicine)

  • DingDing Cai

    (Huaqiao University)

  • Huifang Wang

    (Huaqiao University)

  • Mario P. S. Chin

    (Huaqiao University)

  • James A. Timmons

    (Augur Precision Medicine LTD, Scion House, Stirling University Innovation Park)

  • Claes Wahlestedt

    (University of Miami Miller School of Medicine)

  • Philipp Kapranov

    (Huaqiao University)

Abstract

Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.

Suggested Citation

  • Huifen Cao & Lorena Salazar-García & Fan Gao & Thor Wahlestedt & Chun-Lin Wu & Xueer Han & Ye Cai & Dongyang Xu & Fang Wang & Lu Tang & Natalie Ricciardi & DingDing Cai & Huifang Wang & Mario P. S. Ch, 2019. "Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13602-7
    DOI: 10.1038/s41467-019-13602-7
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    Cited by:

    1. Simon D. Schwarz & Jianming Xu & Kapila Gunasekera & David Schürmann & Cathrine B. Vågbø & Elena Ferrari & Geir Slupphaug & Michael O. Hottiger & Primo Schär & Roland Steinacher, 2024. "Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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