XAB2 dynamics during DNA damage-dependent transcription inhibition
- 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
Giuseppina Giglia-Mari
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.
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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XAB2 dynamics during DNA damage-dependent transcription inhibition
eLife 11:e77094.
https://doi.org/10.7554/eLife.77094
Further reading
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