XAB2 dynamics during DNA damage-dependent transcription inhibition

  1. Lise-Marie Donnio  Is a corresponding author
  2. Elena Cerutti
  3. Charlene Magnani
  4. Damien Neuillet
  5. Pierre-Olivier Mari
  6. Giuseppina Giglia-Mari  Is a corresponding author
  1. CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, France

Abstract

Xeroderma Pigmentosum group A-binding protein 2 (XAB2) is a multi-functional protein playing a critical role in distinct cellular processes including transcription, splicing, DNA repair and mRNA export. In this study, we demonstrate that XAB2 is involved specifically and exclusively in Transcription-Coupled Nucleotide Excision Repair (TC-NER) reactions and solely for RNA Polymerase 2 transcribed genes. Surprisingly, contrary to all the other NER proteins studied so far, XAB2 does not accumulate on the local UV-C damage; on the contrary, it becomes more mobile after damage induction. XAB2 mobility is restored when DNA repair reactions are completed. By scrutinizing from which cellular complex/partner/structure XAB2 is released, we have identified that XAB2 is detached after DNA damage induction from DNA:RNA hybrids, commonly known as R-loops, and from the CSA and XPG proteins. This release contributes to the DNA damage recognition step during TC-NER, as in the absence of XAB2, RNAP2 is blocked longer on UV lesions. Moreover, we also demonstrate that XAB2 has a role in retaining RNAP2 on its substrate without any DNA damage.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file

Article and author information

Author details

  1. Lise-Marie Donnio

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    For correspondence
    lise-marie.donnio@live.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2414-6034
  2. Elena Cerutti

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4644-4817
  3. Charlene Magnani

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Damien Neuillet

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Pierre-Olivier Mari

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Giuseppina Giglia-Mari

    Institut NeuroMyogène (INMG), CNRS UMR 5310, INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France
    For correspondence
    ambra.mari@univ-lyon1.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2001-1965

Funding

Agence Nationale de la Recherche (ANR-14-CE10-0009)

  • Giuseppina Giglia-Mari

Institut National Du Cancer (PLBIO17-043)

  • Giuseppina Giglia-Mari

Institut National Du Cancer (PLBIO19-126)

  • Giuseppina Giglia-Mari

Ligue Contre le Cancer (218398)

  • Giuseppina Giglia-Mari

Electricité de France (218398)

  • Giuseppina Giglia-Mari

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wolf-Dietrich Heyer, University of California, Davis, United States

Publication history

  1. Received: January 25, 2022
  2. Accepted: July 25, 2022
  3. Accepted Manuscript published: July 26, 2022 (version 1)

Copyright

© 2022, Donnio et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lise-Marie Donnio
  2. Elena Cerutti
  3. Charlene Magnani
  4. Damien Neuillet
  5. Pierre-Olivier Mari
  6. Giuseppina Giglia-Mari
(2022)
XAB2 dynamics during DNA damage-dependent transcription inhibition
eLife 11:e77094.
https://doi.org/10.7554/eLife.77094

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