TY - JOUR TI - XAB2 dynamics during DNA damage-dependent transcription inhibition AU - Donnio, Lise-Marie AU - Cerutti, Elena AU - Magnani, Charlene AU - Neuillet, Damien AU - Mari, Pierre-Olivier AU - Giglia-Mari, Giuseppina A2 - Heyer, Wolf-Dietrich A2 - Struhl, Kevin VL - 11 PY - 2022 DA - 2022/07/26 SP - e77094 C1 - eLife 2022;11:e77094 DO - 10.7554/eLife.77094 UR - https://doi.org/10.7554/eLife.77094 AB - Xeroderma Pigmentosum group A-binding protein 2 (XAB2) is a multifunctional protein playing a critical role in distinct cellular processes including transcription, splicing, DNA repair, and messenger RNA 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 (RNAP2)-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. KW - XAB2 KW - TC-NER KW - CSA KW - R-loops KW - pre-mRNA splicing KW - RNA polymerase 2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -