Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation

Swagat Ray, Tatiana Panova, Gail Miller, Arsen Volkov, Andrew C. G. Porter, Jackie Russell, Konstantin I. Panov () and Joost C. B. M. Zomerdijk ()
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Swagat Ray: School of Biological Sciences and the Centre for Cancer Research and Cell Biology, Queen’s University Belfast
Tatiana Panova: School of Biological Sciences and the Centre for Cancer Research and Cell Biology, Queen’s University Belfast
Gail Miller: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee
Arsen Volkov: Gene Targeting Group, Centre for Haematology, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, UK
Andrew C. G. Porter: Gene Targeting Group, Centre for Haematology, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, UK
Jackie Russell: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee
Konstantin I. Panov: School of Biological Sciences and the Centre for Cancer Research and Cell Biology, Queen’s University Belfast
Joost C. B. M. Zomerdijk: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer drugs. Here we uncover a role for topoisomerase IIα in RNA polymerase I-directed ribosomal RNA gene transcription, which drives cell growth and proliferation and is upregulated in cancer cells. Our data suggest that topoisomerase IIα is a component of the initiation-competent RNA polymerase Iβ complex and interacts directly with RNA polymerase I-associated transcription factor RRN3, which targets the polymerase to promoter-bound SL1 in pre-initiation complex formation. In cells, activation of rDNA transcription is reduced by inhibition or depletion of topoisomerase II, and this is accompanied by reduced transient double-strand DNA cleavage in the rDNA-promoter region and reduced pre-initiation complex formation. We propose that topoisomerase IIα functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.

Date: 2013
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DOI: 10.1038/ncomms2599

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