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The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II

Author

Listed:
  • Yana van der Weegen

    (Leiden University Medical Center)

  • Hadar Golan-Berman

    (The Hebrew University of Jerusalem)

  • Tycho E. T. Mevissen

    (Harvard Medical School)

  • Katja Apelt

    (Leiden University Medical Center)

  • Román González-Prieto

    (Leiden University Medical Center)

  • Joachim Goedhart

    (University of Amsterdam)

  • Elisheva E. Heilbrun

    (The Hebrew University of Jerusalem)

  • Alfred C. O. Vertegaal

    (Leiden University Medical Center)

  • Diana van den Heuvel

    (Leiden University Medical Center)

  • Johannes C. Walter

    (Harvard Medical School)

  • Sheera Adar

    (The Hebrew University of Jerusalem)

  • Martijn S. Luijsterburg

    (Leiden University Medical Center)

Abstract

The response to DNA damage-stalled RNA polymerase II (RNAPIIo) involves the assembly of the transcription-coupled repair (TCR) complex on actively transcribed strands. The function of the TCR proteins CSB, CSA and UVSSA and the manner in which the core DNA repair complex, including transcription factor IIH (TFIIH), is recruited are largely unknown. Here, we define the assembly mechanism of the TCR complex in human isogenic knockout cells. We show that TCR is initiated by RNAPIIo-bound CSB, which recruits CSA through a newly identified CSA-interaction motif (CIM). Once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo. Importantly, we find that UVSSA is the key factor that recruits the TFIIH complex in a manner that is stimulated by CSB and CSA. Together these findings identify a sequential and highly cooperative assembly mechanism of TCR proteins and reveal the mechanism for TFIIH recruitment to DNA damage-stalled RNAPIIo to initiate repair.

Suggested Citation

  • Yana van der Weegen & Hadar Golan-Berman & Tycho E. T. Mevissen & Katja Apelt & Román González-Prieto & Joachim Goedhart & Elisheva E. Heilbrun & Alfred C. O. Vertegaal & Diana van den Heuvel & Johann, 2020. "The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15903-8
    DOI: 10.1038/s41467-020-15903-8
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    Cited by:

    1. Chunli Yan & Thomas Dodd & Jina Yu & Bernice Leung & Jun Xu & Juntaek Oh & Dong Wang & Ivaylo Ivanov, 2021. "Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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