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

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          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.

          Abstract

          Topoisomerases facilitate the progress of elongating polymerases during transcription. Zomerdijk and colleagues now demonstrate an additional role for this enzyme; their data suggest that Top2 can cleave DNA inducing topological changes at the ribosomal DNA promoter, which assists de novo assembly of the RNA polymerase I pre-initiation complex.

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          Author and article information

          Journal
          Nat Commun
          Nat Commun
          Nature Communications
          Nature Pub. Group
          2041-1723
          19 March 2013
          : 4
          : 1598
          Affiliations
          [1 ]School of Biological Sciences and the Centre for Cancer Research and Cell Biology, Queen’s University Belfast , Belfast BT9 7BL, UK
          [2 ]Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee , Dundee DD1 5EH, UK
          [3 ]Gene Targeting Group, Centre for Haematology, Imperial College Faculty of Medicine , Du Cane Road, London W12 0NN, UK
          [4 ]These authors contributed equally to this work
          Author notes
          Article
          ncomms2599
          10.1038/ncomms2599
          3615473
          23511463
          4f733d81-9c2a-481b-9d13-359c400b7f98
          Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

          This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

          History
          : 23 November 2012
          : 09 February 2013
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