{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:11:12Z","timestamp":1783728672476,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DBT\/Wellcome Trust India","award":["IA\/I\/14\/1\/501287"],"award-info":[{"award-number":["IA\/I\/14\/1\/501287"]}]},{"DOI":"10.13039\/501100001342","name":"DST","doi-asserted-by":"publisher","award":["EMR\/2016\/001593"],"award-info":[{"award-number":["EMR\/2016\/001593"]}],"id":[{"id":"10.13039\/501100001342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mammalian cells immediately inhibit transcription upon exposure to genotoxic stress to avoid fatal collision between ongoing transcription and newly recruited DNA repair machineries to protect genomic integrity. However, mechanisms of this early transcriptional inhibition are poorly understood. In this study, we decipher a novel role of human EAF1, a positive regulator of ELL-dependent RNA Polymerase II-mediated transcription in vitro, in regulation of temporal inhibition of transcription during genotoxic stress. Our results show that, besides Super Elongation Complex (SEC) and Little Elongation Complex (LEC), human ELL (aka ELL1) also forms a complex with EAF1 alone. Interestingly, contrary to the in vitro studies, EAF1 inhibits ELL-dependent RNA polymerase II-mediated transcription of diverse target genes. Mechanistically, we show that intrinsic self-association property of ELL leads to its reduced interaction with other SEC components. EAF1 enhances ELL self-association and thus reduces its interaction with other SEC components leading to transcriptional inhibition. Physiologically, we show that upon exposure to genotoxic stress, ATM-mediated ELL phosphorylation-dependent enhanced EAF1 association results in reduced ELL interaction with other SEC components that lead to global transcriptional inhibition. Thus, we describe an important mechanism of dynamic transcriptional regulation during genotoxic stress involving post-translational modification of a key elongation factor.<\/jats:p>","DOI":"10.1093\/nar\/gkac943","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T15:39:27Z","timestamp":1666971567000},"page":"10995-11012","source":"Crossref","is-referenced-by-count":11,"title":["ATM-mediated ELL phosphorylation enhances its self-association through increased EAF1 interaction and inhibits global transcription during genotoxic stress"],"prefix":"10.1093","volume":"50","author":[{"given":"Sujay","family":"Pal","sequence":"first","affiliation":[{"name":"Laboratory of Transcription Biology, Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology ,\u00a04, Raja S. C. Mullick Road , Kolkata \u00a0- 32, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad \u00a0201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipika","family":"Yadav","sequence":"additional","affiliation":[{"name":"Laboratory of Transcription Biology, Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology ,\u00a04, Raja S. C. Mullick Road , Kolkata \u00a0- 32, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-6398","authenticated-orcid":false,"given":"Debabrata","family":"Biswas","sequence":"additional","affiliation":[{"name":"Laboratory of Transcription Biology, Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology ,\u00a04, Raja S. C. Mullick Road , Kolkata \u00a0- 32, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad \u00a0201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"2023051710512594900_B1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.yexcr.2014.07.017","article-title":"Blurring the line between the DNA damage response and transcription: the importance of chromatin dynamics","volume":"329","author":"Adam","year":"2014","journal-title":"Exp. Cell. Res."},{"key":"2023051710512594900_B2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.tibs.2018.02.010","article-title":"The cellular response to transcription-blocking DNA damage","volume":"43","author":"Gregersen","year":"2018","journal-title":"Trends Biochem. 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