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Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair

Author

Listed:
  • Cristina Ribeiro-Silva

    (University Medical Center Rotterdam)

  • Mariangela Sabatella

    (University Medical Center Rotterdam
    Princess Máxima Center for pediatric oncology)

  • Angela Helfricht

    (University Medical Center Rotterdam)

  • Jurgen A. Marteijn

    (University Medical Center Rotterdam)

  • Arjan F. Theil

    (University Medical Center Rotterdam)

  • Wim Vermeulen

    (University Medical Center Rotterdam)

  • Hannes Lans

    (University Medical Center Rotterdam)

Abstract

DNA damage sensors DDB2 and XPC initiate global genome nucleotide excision repair (NER) to protect DNA from mutagenesis caused by helix-distorting lesions. XPC recognizes helical distortions by binding to unpaired ssDNA opposite DNA lesions. DDB2 binds to UV-induced lesions directly and facilitates efficient recognition by XPC. We show that not only lesion-binding but also timely DDB2 dissociation is required for DNA damage handover to XPC and swift progression of the multistep repair reaction. DNA-binding-induced DDB2 ubiquitylation and ensuing degradation regulate its homeostasis to prevent excessive lesion (re)binding. Additionally, damage handover from DDB2 to XPC coincides with the arrival of the TFIIH complex, which further promotes DDB2 dissociation and formation of a stable XPC-TFIIH damage verification complex. Our results reveal a reciprocal coordination between DNA damage recognition and verification within NER and illustrate that timely repair factor dissociation is vital for correct spatiotemporal control of a multistep repair process.

Suggested Citation

  • Cristina Ribeiro-Silva & Mariangela Sabatella & Angela Helfricht & Jurgen A. Marteijn & Arjan F. Theil & Wim Vermeulen & Hannes Lans, 2020. "Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18705-0
    DOI: 10.1038/s41467-020-18705-0
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    Cited by:

    1. Namrata Kumar & Arjan F. Theil & Vera Roginskaya & Yasmin Ali & Michael Calderon & Simon C. Watkins & Ryan P. Barnes & Patricia L. Opresko & Alex Pines & Hannes Lans & Wim Vermeulen & Bennett Houten, 2022. "Global and transcription-coupled repair of 8-oxoG is initiated by nucleotide excision repair proteins," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Charlotte Blessing & Katja Apelt & Diana Heuvel & Claudia Gonzalez-Leal & Magdalena B. Rother & Melanie Woude & Román González-Prieto & Adi Yifrach & Avital Parnas & Rashmi G. Shah & Tia Tyrsett Kuo &, 2022. "XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Kook Son & Vakil Takhaveev & Visesato Mor & Hobin Yu & Emma Dillier & Nicola Zilio & Nikolai J. L. Püllen & Dmitri Ivanov & Helle D. Ulrich & Shana J. Sturla & Orlando D. Schärer, 2024. "Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. 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.

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