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CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential

Author

Listed:
  • Youtao Lu

    (University of Pennsylvania)

  • Jaehee Lee

    (University of Pennsylvania)

  • Jifen Li

    (University of Pennsylvania)

  • Srinivasa Rao Allu

    (University of Pennsylvania)

  • Jinhui Wang

    (University of Pennsylvania)

  • HyunBum Kim

    (University of Pennsylvania)

  • Kevin L. Bullaughey

    (University of Pennsylvania)

  • Stephen A. Fisher

    (University of Pennsylvania)

  • C. Erik Nordgren

    (University of Pennsylvania)

  • Jean G. Rosario

    (University of Pennsylvania)

  • Stewart A. Anderson

    (Children’s Hospital of Philadelphia)

  • Alexandra V. Ulyanova

    (University of Pennsylvania)

  • Steven Brem

    (University of Pennsylvania)

  • H. Isaac Chen

    (University of Pennsylvania)

  • John A. Wolf

    (University of Pennsylvania)

  • M. Sean Grady

    (University of Pennsylvania)

  • Sergei A. Vinogradov

    (University of Pennsylvania)

  • Junhyong Kim

    (University of Pennsylvania)

  • James Eberwine

    (University of Pennsylvania)

Abstract

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe “CHEX-seq” which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3’-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape. CHEX-seq is benchmarked in human K562 cells, and its utilities are demonstrated in cultures of mouse and human brain cells as well as immunostained spatially localized neurons in brain sections. The amount of ssDNA is dynamically regulated in response to perturbation. CHEX-seq also identifies single-stranded regions of mitochondrial DNA in single cells. Surprisingly, CHEX-seq identifies single-stranded loci in mouse and human gDNA that catalyze porphyrin metalation in vitro, suggesting a catalytic activity for genomic ssDNA. We posit that endogenous DNA enzymatic activity is a function of genomic ssDNA.

Suggested Citation

  • Youtao Lu & Jaehee Lee & Jifen Li & Srinivasa Rao Allu & Jinhui Wang & HyunBum Kim & Kevin L. Bullaughey & Stephen A. Fisher & C. Erik Nordgren & Jean G. Rosario & Stewart A. Anderson & Alexandra V. U, 2023. "CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43158-6
    DOI: 10.1038/s41467-023-43158-6
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    References listed on IDEAS

    as
    1. Wenfei Jin & Qingsong Tang & Mimi Wan & Kairong Cui & Yi Zhang & Gang Ren & Bing Ni & Jeffrey Sklar & Teresa M. Przytycka & Richard Childs & David Levens & Keji Zhao, 2015. "Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples," Nature, Nature, vol. 528(7580), pages 142-146, December.
    2. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    3. Jason D. Buenrostro & Beijing Wu & Ulrike M. Litzenburger & Dave Ruff & Michael L. Gonzales & Michael P. Snyder & Howard Y. Chang & William J. Greenleaf, 2015. "Single-cell chromatin accessibility reveals principles of regulatory variation," Nature, Nature, vol. 523(7561), pages 486-490, July.
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    Cited by:

    1. Aris A. Polyzos & Ana Cheong & Jung Hyun Yoo & Lana Blagec & Sneh M. Toprani & Zachary D. Nagel & Cynthia T. McMurray, 2024. "Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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