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A damaged genome’s transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks

Author

Listed:
  • Fabio Iannelli

    (IFOM, The FIRC Institute of Molecular Oncology)

  • Alessandro Galbiati

    (IFOM, The FIRC Institute of Molecular Oncology)

  • Ilaria Capozzo

    (IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche))

  • Quan Nguyen

    (RIKEN Center for Life Science Technologies)

  • Brian Magnuson

    (University of Michigan)

  • Flavia Michelini

    (IFOM, The FIRC Institute of Molecular Oncology)

  • Giuseppina D’Alessandro

    (IFOM, The FIRC Institute of Molecular Oncology)

  • Matteo Cabrini

    (IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche))

  • Marco Roncador

    (IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche))

  • Sofia Francia

    (IFOM, The FIRC Institute of Molecular Oncology
    IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche))

  • Nicola Crosetto

    (Science for Life Laboratory, Karolinska Institutet)

  • Mats Ljungman

    (University of Michigan)

  • Piero Carninci

    (RIKEN Center for Life Science Technologies)

  • Fabrizio d’Adda di Fagagna

    (IFOM, The FIRC Institute of Molecular Oncology
    IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche))

Abstract

Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.

Suggested Citation

  • Fabio Iannelli & Alessandro Galbiati & Ilaria Capozzo & Quan Nguyen & Brian Magnuson & Flavia Michelini & Giuseppina D’Alessandro & Matteo Cabrini & Marco Roncador & Sofia Francia & Nicola Crosetto & , 2017. "A damaged genome’s transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15656
    DOI: 10.1038/ncomms15656
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    Cited by:

    1. Yuqi Shen & Kinam Gupta & Sue Mei Tan-Wong & Sean Wen & Christopher A. Fisher & Liezel Tamon & Nicholas J. Proudfoot & Richard J. Gibbons & Douglas R. Higgs, 2026. "ATRX loss couples genome instability at a G-rich repeat to dysregulation of human alpha-globin expression," Nature Communications, Nature, vol. 17(1), pages 1-14, December.
    2. Amador Romero-Franco & Cintia Checa-Rodríguez & Sonia Jimeno & Maikel Castellano-Pozo & Paula Aguilera & Hector Miras & Amadeo Wals & Silvia Jimeno-González & Andres Joaquin Lopez-Contreras & Pablo Hu, 2025. "Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    3. Daniel Gómez-Cabello & George Pappas & Diana Aguilar-Morante & Christoffel Dinant & Jiri Bartek, 2022. "CtIP-dependent nascent RNA expression flanking DNA breaks guides the choice of DNA repair pathway," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Adele Alagia & Kamal Ajit & Arianna Fazio & Qilin Long & Monika Gullerova, 2025. "NSUN2 facilitates DICER cleavage of DNA damage-associated R-loops to promote repair," Nature Communications, Nature, vol. 16(1), pages 1-20, December.

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