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

15 Citations (Scopus)

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.
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
Ribosomal RNA
cancer
DNA
Cell proliferation
Cell growth
DNA-Directed RNA Polymerases
ribonucleic acids
rRNA Genes
Genetic Promoter Regions

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 - 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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