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A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair

Author

Listed:
  • Diana Heuvel

    (Leiden University Medical Center)

  • Cornelia G. Spruijt

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen
    Prinses Maxima Center)

  • Román González-Prieto

    (Leiden University Medical Center)

  • Angela Kragten

    (Leiden University Medical Center)

  • Michelle T. Paulsen

    (University of Michigan)

  • Di Zhou

    (Oncode Institute)

  • Haoyu Wu

    (Leiden University Medical Center)

  • Katja Apelt

    (Leiden University Medical Center)

  • Yana Weegen

    (Leiden University Medical Center)

  • Kevin Yang

    (University of Michigan
    University of Michigan)

  • Madelon Dijk

    (Leiden University Medical Center)

  • Lucia Daxinger

    (Leiden University Medical Center)

  • Jurgen A. Marteijn

    (Oncode Institute)

  • Alfred C. O. Vertegaal

    (Leiden University Medical Center)

  • Mats Ljungman

    (University of Michigan
    University of Michigan)

  • Michiel Vermeulen

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Martijn S. Luijsterburg

    (Leiden University Medical Center)

Abstract

Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. Although dispensable for TCR-mediated repair, PAF1C is essential for transcription recovery after UV irradiation. We find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.

Suggested Citation

  • Diana Heuvel & Cornelia G. Spruijt & Román González-Prieto & Angela Kragten & Michelle T. Paulsen & Di Zhou & Haoyu Wu & Katja Apelt & Yana Weegen & Kevin Yang & Madelon Dijk & Lucia Daxinger & Jurgen, 2021. "A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21520-w
    DOI: 10.1038/s41467-021-21520-w
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    Cited by:

    1. Negin Khosraviani & V. Talya Yerlici & Jonathan St-Germain & Yi Yang Hou & Shi Bo Cao & Carla Ghali & Michael Bokros & Rehna Krishnan & Razqallah Hakem & Stephen Lee & Brian Raught & Karim Mekhail, 2024. "Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Diana A. Llerena Schiffmacher & Shun-Hsiao Lee & Katarzyna W. Kliza & Arjan F. Theil & Masaki Akita & Angela Helfricht & Karel Bezstarosti & Camila Gonzalo-Hansen & Haico Attikum & Matty Verlaan-de Vr, 2024. "The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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