SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:su-135980"
 

Search: onr:"swepub:oai:DiVA.org:su-135980" > Inhibition of RNA p...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling

Quin, Jaclyn (author)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Peter MacCallum Cancer Centre, Australia; University of Melbourne, Australia
Chan, Keefe T. (author)
Devlin, Jennifer R. (author)
show more...
Cameron, Donald P. (author)
Diesch, Jeannine (author)
Cullinane, Carleen (author)
Ahern, Jessica (author)
Khot, Amit (author)
Hein, Nadine (author)
George, Amee J. (author)
Hannan, Katherine M. (author)
Poortinga, Gretchen (author)
Sheppard, Karen E. (author)
Khanna, Kum Kum (author)
Johnstone, Ricky W. (author)
Drygin, Denis (author)
McArthur, Grant A. (author)
Pearson, Richard B. (author)
Sanij, Elaine (author)
Hannan, Ross D. (author)
show less...
 (creator_code:org_t)
2016-07-06
2016
English.
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:31, s. 49800-49818
Related links:
https://doi.org/10.1...
show more...
http://www.oncotarge...
https://urn.kb.se/re...
https://doi.org/10.1...
show less...
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • RNA polymerase I (Pol I)-mediated transcription of the ribosomal RNA genes (rDNA) is confined to the nucleolus and is a rate-limiting step for cell growth and proliferation. Inhibition of Pol I by CX-5461 can selectively induce p53-mediated apoptosis of tumour cells in vivo. Currently, CX-5461 is in clinical trial for patients with advanced haematological malignancies (Peter Mac, Melbourne). Here we demonstrate that CX-5461 also induces p53-independent cell cycle checkpoints mediated by ATM/ATR signaling in the absence of DNA damage. Further, our data demonstrate that the combination of drugs targeting ATM/ATR signaling and CX-5461 leads to enhanced therapeutic benefit in treating p53-null tumours in vivo, which are normally refractory to each drug alone. Mechanistically, we show that CX-5461 induces an unusual chromatin structure in which transcriptionally competent relaxed rDNA repeats are devoid of transcribing Pol I leading to activation of ATM signaling within the nucleoli. Thus, we propose that acute inhibition of Pol transcription initiation by CX-5461 induces a novel nucleolar stress response that can be targeted to improve therapeutic efficacy.

Subject headings

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

RNA polymerase I
rDNA
CX-5461
nucleolar stress response
DNA damage signaling

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

  • Oncotarget (Search for host publication in LIBRIS)

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view