scholarly journals Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Swagat Ray ◽  
Tatiana Panova ◽  
Gail Miller ◽  
Arsen Volkov ◽  
Andrew C. G. Porter ◽  
...  
Keyword(s):  
Complex Formation ◽  
Rna Polymerase ◽  
Rna Polymerase I ◽  
Initiation Complex ◽  
Topoisomerase Iiα ◽  
Polymerase I

scholarly journals TBP-TAF Complex SL1 Directs RNA Polymerase I Pre-initiation Complex Formation and Stabilizes Upstream Binding Factor at the rDNA Promoter

2005 ◽  
Vol 280 (33) ◽  
pp. 29551-29558 ◽  
Author(s):  
J. Karsten Friedrich ◽  
Kostya I. Panov ◽  
Pavel Cabart ◽  
Jackie Russell ◽  
Joost C. B. M. Zomerdijk
Keyword(s):  
Complex Formation ◽  
Rna Polymerase ◽  
Rna Polymerase I ◽  
Initiation Complex ◽  
Binding Factor ◽  
Upstream Binding Factor ◽  
Polymerase I

scholarly journals The yeast RNA polymerase I promoter: ribosomal DNA sequences involved in transcription initiation and complex formation inin vitro

1991 ◽  
Vol 19 (19) ◽  
pp. 5363-5370 ◽  
Author(s):  
Tanja Kulkens ◽  
Daniel L. Riggs ◽  
J.Danis Heck ◽  
Rudi J. Planta ◽  
Masayasu Nomura
Keyword(s):  
Complex Formation ◽  
Rna Polymerase ◽  
Ribosomal Dna ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Rna Polymerase I ◽  
Polymerase I

scholarly journals The chemotherapeutic agent CX-5461 irreversibly blocks RNA polymerase I initiation and promoter release to cause nucleolar disruption, DNA damage and cell inviability

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Jean-Clément Mars ◽  
Michel G Tremblay ◽  
Mélissa Valere ◽  
Dany S Sibai ◽  
Marianne Sabourin-Felix ◽  
...  
Keyword(s):  
Dna Damage ◽  
Rna Polymerase ◽  
Ribosomal Rna ◽  
Transcription Initiation ◽  
Ribosome Biogenesis ◽  
Chemotherapeutic Agent ◽  
Rna Polymerase I ◽  
Initiation Complex ◽  
Promoter Recruitment ◽  
Polymerase I

Abstract In the search for drugs to effectively treat cancer, the last 10 years have seen a resurgence of interest in targeting ribosome biogenesis. CX-5461 is a potential inhibitor of ribosomal RNA synthesis that is now showing promise in phase I trials as a chemotherapeutic agent for a range of malignancies. Here, we show that CX-5461 irreversibly inhibits ribosomal RNA transcription by arresting RNA polymerase I (RPI/Pol1/PolR1) in a transcription initiation complex. CX-5461 does not achieve this by preventing formation of the pre-initiation complex nor does it affect the promoter recruitment of the SL1 TBP complex or the HMGB-box upstream binding factor (UBF/UBTF). CX-5461 also does not prevent the subsequent recruitment of the initiation-competent RPI–Rrn3 complex. Rather, CX-5461 blocks promoter release of RPI–Rrn3, which remains irreversibly locked in the pre-initiation complex even after extensive drug removal. Unexpectedly, this results in an unproductive mode of RPI recruitment that correlates with the onset of nucleolar stress, inhibition of DNA replication, genome-wide DNA damage and cellular senescence. Our data demonstrate that the cytotoxicity of CX-5461 is at least in part the result of an irreversible inhibition of RPI transcription initiation and hence are of direct relevance to the design of improved strategies of chemotherapy.

scholarly journals Formation of the transcription initiation complex on mammalian rDNA.

1986 ◽  
Vol 6 (10) ◽  
pp. 3418-3427 ◽  
Author(s):  
H Kato ◽  
M Nagamine ◽  
R Kominami ◽  
M Muramatsu
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Short Pulse ◽  
Rna Polymerase I ◽  
Rrna Gene ◽  
Preinitiation Complex ◽  
Initiation Complex ◽  
Transcription Initiation Complex ◽  
Polymerase I

Steps for the formation of transcription initiation complex on the human rRNA gene (rDNA) in vitro were analyzed with partially purified transcription factors and RNA polymerase I. The reaction requires at least two factors besides RNA polymerase I for maximal efficiency. Preincubation and short-pulse analyses of the accurate transcripts revealed the following steps. First, the species-dependent factor, designated TFID, bound to the rDNA template, forming a preinitiation complex (PIC-1) which was resistant to a moderate concentration (0.015 to 0.02%) of Sarkosyl. Other factors, designated TFIA and RNA polymerase I, were then added to convert it to the final preinitiation complex PIC-3. This complex incorporated the first two nucleoside triphosphates of the starting site to complete the initiation complex (IC), which was resistant to a high concentration (0.2%) of Sarkosyl. Binding of TFID was rate limiting in the overall initiation reaction in vitro. Together with the kinetics of incorporation, the results are interpreted to mean that TFID, one bound, remains complexed with rDNA together with TFIA as the PIC-2 for many rounds of transcription by RNA polymerase I. Thus, the formation of PIC-2 may be a prerequisite for the stable opening of rDNA for transcription in vivo.

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