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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.<\/jats:p>","DOI":"10.7554\/elife.77094","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T08:00:51Z","timestamp":1658822451000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.77094","source":"Crossref","is-referenced-by-count":14,"title":["XAB2 dynamics during DNA damage-dependent transcription inhibition"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-6034","authenticated-orcid":true,"given":"Lise-Marie","family":"Donnio","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0322sf130","id-type":"ROR","asserted-by":"publisher"}],"name":"Institut NeuroMyog\u00e8ne (INMG), CNRS UMR 5310, INSERM U1217, Universit\u00e9 Claude Bernard Lyon 1","place":["Lyon, 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