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, Joost C B M Zomerdijk

Research output: Contribution to journalArticle

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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 IIa 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 IIa is a component of the initiation-competent RNA polymerase Iß 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 IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.
Original languageEnglish
Article number1598
Number of pages12
JournalNature Communications
Volume4
DOIs
Publication statusPublished - 19 Mar 2013

Fingerprint

RNA Polymerase I
Type II DNA Topoisomerase
Transcription
Ribosomal DNA
Chemical activation
activation
Pol1 Transcription Initiation Complex Proteins
deoxyribonucleic acid
strands
cleavage
DNA Cleavage
cancer
ribonucleic acids
rRNA Genes
Genetic Promoter Regions
Transcriptional Activation
Ribosomal RNA
Ligation
DNA
Neoplasms

Cite this

Ray, Swagat ; Panova, Tatiana ; Miller, Gail ; Volkov, Arsen ; Porter, Andrew C G ; Russell, Jackie ; Panov, Konstantin I ; Zomerdijk, Joost C B M. / Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation. In: Nature Communications. 2013 ; Vol. 4.
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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 IIa 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 IIa is a component of the initiation-competent RNA polymerase I{\ss} 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 IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.",
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Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation. / Ray, Swagat; Panova, Tatiana; Miller, Gail; Volkov, Arsen; Porter, Andrew C G; Russell, Jackie; Panov, Konstantin I; Zomerdijk, Joost C B M.

In: Nature Communications, Vol. 4, 1598, 19.03.2013.

Research output: Contribution to journalArticle

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AU - Panova, Tatiana

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AU - Russell, Jackie

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AB - 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 IIa 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 IIa is a component of the initiation-competent RNA polymerase Iß 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 IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.

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