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