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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,3,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Cellular NF-\u03baB activity is stringently regulated. Constitutive NF-\u03baB activation (NF-\u03baB\n                    <jats:sup>CA<\/jats:sup>\n                    ), however, frequently occurs in T\/B cell malignancies including adult T cell leukemia (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We demonstrate that NF-\u03baB\n                    <jats:sup>CA<\/jats:sup>\n                    via the HTLV-1 trans-activator\/oncoprotein Tax causes R-loop accumulation, DNA double-strand breaks, and senescence and that R-loop processing by the transcription-coupled nucleotide excision repair (TC-NER) pathway contributes to senescence induction. We show that TC-NER deficits occur in ATL. They enable senescence escape and outgrowth of HTLV-1\u2013infected and ATL cells with NF-\u03baB\n                    <jats:sup>CA<\/jats:sup>\n                    , but render ATL cells hypersensitive to ultraviolet light. With NF-\u03baB\n                    <jats:sup>CA<\/jats:sup>\n                    , ATL cells continue to accumulate abundant R-loops. TC-NER deficiency and excess R-loop accumulation represent vulnerabilities of ATL that can be exploited therapeutically.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2005568118","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T16:30:48Z","timestamp":1614616248000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["NF-\u03baB\u2013induced R-loop accumulation and DNA damage select for nucleotide excision repair deficiencies in adult T cell leukemia"],"prefix":"10.1073","volume":"118","author":[{"given":"Yunlong","family":"He","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagesh","family":"Pasupala","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijun","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batsuhk","family":"Dorjbal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Ming","family":"Shih","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan;"},{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County 350, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-6218","authenticated-orcid":false,"given":"Sharmistha","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopa","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-6320","authenticated-orcid":false,"given":"Milos","family":"Miljkovic","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9927-4869","authenticated-orcid":false,"given":"Oliver John","family":"Semmes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501;"},{"name":"The Leroy T. 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