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DNA topoisomerase IIα is required for RNA polymerase II transcription on chromatin templates

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  • Neelima Mondal

    (Brigham and Women's Hospital, Harvard Medical School)

  • Jeffrey D. Parvin

    (Brigham and Women's Hospital, Harvard Medical School)

Abstract

In the nucleus of the cell, core RNA polymerase II (pol II) is associated with a large complex called the pol II holoenzyme (holo-pol)1,2. Transcription by core pol II in vitro on nucleosomal templates is repressed compared with that on templates of histone-free naked DNA3,4,5. We found that the transcriptional activity of holo-pol, in contrast to that of core pol II, is not markedly repressed on chromatin templates. We refer to this property of holo-pol as chromatin-dependent coactivation (CDC). Here we show that DNA topoisomerase IIα is associated with the holo-pol and is a required component of CDC. Etoposide and ICRF-193, specific inhibitors of topoisomerase II, blocked transcription on chromatin templates, but did not affect transcription on naked templates. Addition of purified topoisomerase IIα reconstituted CDC activity in reactions with core pol II. These findings suggest that transcription on chromatin templates results in the accumulation of superhelical tension, making the relaxation activity of topoisomerase II essential for productive RNA synthesis on nucleosomal DNA.

Suggested Citation

  • Neelima Mondal & Jeffrey D. Parvin, 2001. "DNA topoisomerase IIα is required for RNA polymerase II transcription on chromatin templates," Nature, Nature, vol. 413(6854), pages 435-438, September.
    • Handle: RePEc:nat:nature:v:413:y:2001:i:6854:d:10.1038_35096590
    DOI: 10.1038/35096590
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    Cited by:

    1. Ian G. Cowell & Caroline A. Austin, 2012. "Mechanism of Generation of Therapy Related Leukemia in Response to Anti-Topoisomerase II Agents," IJERPH, MDPI, vol. 9(6), pages 1-17, May.

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