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Human Topoisomerase II and Transcription

Human Topoisomerase II and Transcription

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

Neelima Mondal & Jeffrey D. Parvin
Department of Pathology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, Massachusetts 02115, USA

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±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 IIa 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 IIa 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.

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Human Topoisomerase II provided by TopoGEN.  Etoposide also available from TopoGEN.

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