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Dissecting regulatory pathways for transcription recovery following DNA damage reveals a non-canonical function of the histone chaperone HIRA

Author

Listed:
  • Déborah Bouvier

    (Université de Paris)

  • Juliette Ferrand

    (Université de Paris)

  • Odile Chevallier

    (Université de Paris)

  • Michelle T. Paulsen

    (University of Michigan)

  • Mats Ljungman

    (University of Michigan)

  • Sophie E. Polo

    (Université de Paris)

Abstract

Transcription restart after a genotoxic challenge is a fundamental yet poorly understood process. Here, we dissect the interplay between transcription and chromatin restoration after DNA damage by focusing on the human histone chaperone complex HIRA, which is required for transcription recovery post UV. We demonstrate that HIRA is recruited to UV-damaged chromatin via the ubiquitin-dependent segregase VCP to deposit new H3.3 histones. However, this local activity of HIRA is dispensable for transcription recovery. Instead, we reveal a genome-wide function of HIRA in transcription restart that is independent of new H3.3 and not restricted to UV-damaged loci. HIRA coordinates with ASF1B to control transcription restart by two independent pathways: by stabilising the associated subunit UBN2 and by reducing the expression of the transcription repressor ATF3. Thus, HIRA primes UV-damaged chromatin for transcription restart at least in part by relieving transcription inhibition rather than by depositing new H3.3 as an activating bookmark.

Suggested Citation

  • Déborah Bouvier & Juliette Ferrand & Odile Chevallier & Michelle T. Paulsen & Mats Ljungman & Sophie E. Polo, 2021. "Dissecting regulatory pathways for transcription recovery following DNA damage reveals a non-canonical function of the histone chaperone HIRA," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24153-1
    DOI: 10.1038/s41467-021-24153-1
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