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Dysregulation of the basal RNA polymerase transcription apparatus in cancer

Journal

NATURE REVIEWS CANCER
Volume 13, Issue 5, Pages 299-314

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nrc3496

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Funding

  1. National Health and Medical Research Council (NHMRC) of Australia programme and project grants
  2. Leukemia Foundation Grant in Aid
  3. Prostate Cancer Foundation of Australia grant in aid
  4. NHMRC Research Fellowship
  5. NHMRC Postgraduate Research Scholarship
  6. GSK Postgraduate Research Scholarship
  7. Leukemia Foundation Postdoctoral Fellowship
  8. Cancer Council of Victoria Sir Edward Weary Dunlop Clinical Research Fellowship
  9. NHMRC Clinical Research Fellowship

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Mutations that directly affect transcription by RNA polymerases rank among the most central mediators of malignant transformation, but the frequency of new anticancer drugs that selectively target defective transcription apparatus entering the clinic has been limited. This is because targeting the large protein-protein and protein-DNA interfaces that control both generic and selective aspects of RNA polymerase transcription has proved extremely difficult. However, recent technological advances have led to a 'quantum leap' in our comprehension of the structure and function of the core RNA polymerase components, how they are dysregulated in a broad range of cancers and how they may be targeted for 'transcription therapy'.

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