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

Quin, Jaclyn; Chan, Keefe; Devlin, Jennifer; Cameron, Donald; Diesch, Jeannine; Cullinane, C; Ahern, Jessica; Khot, Amit; Hein, Nadine; George, Amee; Hannan, Katherine; Poortinga, Gretchen; Sheppard, Karen E.; Khanna, Kum Kum; Johnstone, Ricky; Drygin, Denis; McArthur, Grant; Pearson, Richard B; Sanij, Elaine; Hannan, Ross

Description

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...[Show more]

CollectionsANU Research Publications
Date published: 2016
Type: Journal article
URI: http://hdl.handle.net/1885/153511
Source: Oncotarget
DOI: 10.18632/oncotarget.10452

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