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When defective, TC\u2010NER is causatively associated with Cockayne\u2010Syndrome (CS), a rare severe human progeroid disorder. Although the presence of unresolved transcription\u2010blocking lesions is considered a driver of the aging process, the molecular features of the transcription\u2010driven response to genotoxic stress in CS\u2010B cells remain largely unknown. Here, an in\u2010depth view of the transcriptional and associated chromatin dynamics that occur in CS\u2010B cells illuminates the role of CSB therein. By employing high\u2010throughput genome\u2010wide approaches, we observed that absence of a functional CSB protein results in a delay in transcription progression, more positioned +1 nucleosomes, and less dynamic chromatin structure, compared to normal cells. We found that early after exposure to UV, CS\u2010B cells released RNA polymerase II (RNAPII) from promoter\u2010proximal pause sites into elongation. However, the magnitude of this response and the progression of RNAPII were reduced compared to normal counterparts. Notably, we detected increased post\u2010UV retainment of unprocessed nascent RNA transcripts and chromatin\u2010associated elongating RNAPII molecules. Contrary to the prevailing models, we found that transcription initiation is operational in CS\u2010B fibroblasts early after UV and that chromatin accessibility showed a marginal increase. Our study provides robust evidence for the role of CSB in shaping the transcription and chromatin landscape both in homeostasis and in response to genotoxic insults, which is independent of its known role in TC\u2010NER, and which may underlie major aspects of the CS phenotype.<\/jats:p>","DOI":"10.1111\/acel.14341","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:40:37Z","timestamp":1728283237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cockayne syndrome B protein is implicated in transcription and associated chromatin dynamics in homeostatic and genotoxic conditions"],"prefix":"10.1111","volume":"24","author":[{"given":"Anastasios","family":"Liakos","sequence":"first","affiliation":[{"name":"Institute for Fundamental Biomedical Research BSRC \u201cAlexander Fleming\u201d  Vari Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina 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