title: Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation.
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.
authors.affiliation: School of Biological Sciences and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors.forename: Swagat
authors.initials: S
authors.lastname: Ray
authors.forename: Tatiana
authors.initials: T
authors.lastname: Panova
authors.forename: Gail
authors.initials: G
authors.lastname: Miller
authors.forename: Arsen
authors.initials: A
authors.lastname: Volkov
authors.forename: Andrew C G
authors.initials: AC
authors.lastname: Porter
authors.forename: Jackie
authors.initials: J
authors.lastname: Russell
authors.forename: Konstantin I
authors.initials: KI
authors.lastname: Panov
authors.forename: Joost C B M
authors.initials: JC
authors.lastname: Zomerdijk
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D006868:Hydrolysis; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004247:DNA; D012318:RNA Polymerase I; D004250:DNA Topoisomerases, Type II