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• W2103015871 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. 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 novoassembly of the RNA polymerase I pre-initiation complex." @default.
• W2103015871 created "2016-06-24" @default.
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• W2103015871 date "2013-03-19" @default.
• W2103015871 modified "2023-09-23" @default.
• W2103015871 title "Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation" @default.
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• W2103015871 doi "https://doi.org/10.1038/ncomms2599" @default.
• W2103015871 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3615473" @default.
• W2103015871 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23511463" @default.
• W2103015871 hasPublicationYear "2013" @default.
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