{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:28:13Z","timestamp":1792700893408,"version":"4.5.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5781","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2006,6,23]]},"abstract":"<jats:p>Multiple enzymatic activities are required for transcriptional initiation. The enzyme DNA topoisomerase II associates with gene promoter regions and can generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to know whether this enzyme is critical for regulated gene activation. We report that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase II\u03b2-dependent, transient, site-specific dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate\u2013ribose) polymerase\u20131 enzymatic activity is induced, which is required for a nucleosome-specific histone H1\u2013high-mobility group B exchange event and for local changes of chromatin architecture. Our data mechanistically link DNA topoisomerase II\u03b2\u2013dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription.<\/jats:p>","DOI":"10.1126\/science.1127196","type":"journal-article","created":{"date-parts":[[2006,6,22]],"date-time":"2006-06-22T17:46:04Z","timestamp":1150998364000},"page":"1798-1802","source":"Crossref","is-referenced-by-count":806,"title":["A Topoisomerase II\u00df-Mediated dsDNA Break Required for Regulated Transcription"],"prefix":"10.1126","volume":"312","author":[{"given":"Bong-Gun","family":"Ju","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Medicine, School of Medicine, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093\u20130648, USA."},{"name":"Department of Medicine, Division of Endocrinology, School of Medicine, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093\u20130648, USA."},{"name":"Department of 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Nelson and K. Ohgi for their assistance; S. Ogawa and J. Puc for reagents; and X. Zhu and T. Wang for discussions and advice. We also thank J. Hightower and M. Fisher for assistance in figure and manuscript preparation and M. Gonzalez (Santa Cruz Biotechnology) for advice on reagents. M.G.R. is an investigator with the Howard Hughes Medical Institute and B.J. is supported by the U.S. Army Medical Research and Materiel Command (grant DAMD17-01-1-0184). 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