A Zomerdijk Lab paper published today (19 March 2013) has identified a novel role for DNA topoisomerase II, a clinically relevant anti-cancer drug target, in the regulated expression of ribosomal RNA genes.

The paper, Topoisomerase IIa promotes activation of transcription by RNA Polymerase I by facilitating pre-initiation complex formation, published in Nature Communications is a collaboration between scientist at the Centre for Gene Regulation and Expression at CLS Dundee, Queen’s University, Belfast and Imperial College.

Type II DNA topoisomerases (Top2) produce critical topological changes in localized DNA regions to regulate genome transactions. In this study, we demonstrate a novel role for Top2α in activation of transcription by RNA Polymerase I (Pol I) of the human ribosomal RNA genes. Top2α likely effects DNA topological changes near the start site of transcription that facilitate new assembly of transcription initiation complexes. Top2 inhibitors that are effective anti-cancer drugs can block activation of Pol I transcription independent of DNA damage response pathways. Pol I transcription drives ribosome biogenesis and is intricately linked to cell growth and proliferation and upregulated in cancer cells. We speculate that inhibitors specifically designed to target Top2α in Pol I transcription could be useful non-genotoxic tools in the fight against cancer.


Swagat Ray2, Tatiana Panova1,2, Gail Miller1, Arsen Volkov3, Andrew C.G. Porter3, Jackie Russell1, Konstantin I. Panov1,2, †,* and Joost C.B.M. Zomerdijk1, †,*

1Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK

2School of Biological Sciences and the Centre for Cancer Research and Cell Biology, The Queen’s University Belfast, Belfast, BT9 7BL, UK

3Gene Targeting Group, Centre for Haematology, Imperial College Faculty of Medicine, Du Cane Rd, London W12 0NN, UK.

† These authors contributed equally to this work.