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

TY - JOUR

T1 - Topoisomerase IIα promotes activation of RNA polymerase i transcription by facilitating pre-initiation complex formation

AU - Ray, Swagat

AU - Panova, Tatiana

AU - Miller, Gail

AU - Volkov, Arsen

AU - Porter, Andrew C.G.

AU - Russell, Jackie

AU - Panov, Konstantin I.

AU - Zomerdijk, Joost C.B.M.

N1 - Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/3/19

Y1 - 2013/3/19

N2 - 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.

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.

UR - https://www.scopus.com/pages/publications/84875853142

U2 - 10.1038/ncomms2599

DO - 10.1038/ncomms2599

M3 - Article

C2 - 23511463

AN - SCOPUS:84875853142

SN - 2041-1723

VL - 4

JO - Nature Communications

JF - Nature Communications

M1 - 1598

ER -