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Structural basis of TFIIH activation for nucleotide excision repair

Author

Listed:
  • Goran Kokic

    (Max Planck Institute for Biophysical Chemistry)

  • Aleksandar Chernev

    (Max Planck Institute for Biophysical Chemistry, Bioanalytical Mass Spectrometry
    University Medical Center Göttingen, Institute of Clinical Chemistry, Bioanalytics Group)

  • Dimitry Tegunov

    (Max Planck Institute for Biophysical Chemistry)

  • Christian Dienemann

    (Max Planck Institute for Biophysical Chemistry)

  • Henning Urlaub

    (Max Planck Institute for Biophysical Chemistry, Bioanalytical Mass Spectrometry
    University Medical Center Göttingen, Institute of Clinical Chemistry, Bioanalytics Group)

  • Patrick Cramer

    (Max Planck Institute for Biophysical Chemistry)

Abstract

Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA. Compared to its transcription conformation, the TFIIH structure is rearranged such that its ATPase subunits XPB and XPD bind double- and single-stranded DNA, consistent with their translocase and helicase activities, respectively. XPA releases the inhibitory kinase module of TFIIH, displaces a ‘plug’ element from the DNA-binding pore in XPD, and together with the NER factor XPG stimulates XPD activity. Our results explain how TFIIH is switched from a transcription to a repair factor, and provide the basis for a mechanistic analysis of the NER pathway.

Suggested Citation

  • Goran Kokic & Aleksandar Chernev & Dimitry Tegunov & Christian Dienemann & Henning Urlaub & Patrick Cramer, 2019. "Structural basis of TFIIH activation for nucleotide excision repair," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10745-5
    DOI: 10.1038/s41467-019-10745-5
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    Cited by:

    1. Alba Muniesa-Vargas & Carlota Davó-Martínez & Cristina Ribeiro-Silva & Melanie van der Woude & Karen L. Thijssen & Ben Haspels & David Häckes & Ülkem U. Kaynak & Roland Kanaar & Jurgen A. Marteijn & A, 2024. "Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Jina Yu & Chunli Yan & Thomas Dodd & Chi-Lin Tsai & John A. Tainer & Susan E. Tsutakawa & Ivaylo Ivanov, 2023. "Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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