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Topo II and Topo I are not Equivalent Topological Adjustment Machines in vivo

Topo II and Topo I are not Equivalent Topological Adjustment Machines in vivo

In a recent report in Nucleic Acids Research, researchers provide evidence that topoisomerase I and II perform similar functions in vitro (relaxation of supercoiled DNA); however, the in vivo situation is very different. There are of course non-overlapping activities of type I and II enzymes, specifically, the latter are cell cycle regulated and provide decatenase activity which is essential for life. Still, topo enzymes provide other key functions that attend all aspects of template activation. From genetic complementation studies, topological adjustments associated with transcription and DNA replication can be met with either topo I or II, so the thinking went. In this very elegant report, Joshi, Pina and Roca demonstrate that in budding yeast, deleting topo II effectively depletes (but does not eliminate) long (>3 kb) polyA+ transcripts and this phenotype cannot be rescued by topo I over expression constructs. Only topo II has the ability to promote topological tension that attends RNA polymerase II advancement across long template sections. The authors propose a credible model to explain their findings, which have a basis in early studies on ribosomal RNA expression in topo I and II mutants from R. Sternglanz (Genes Dev. 6: 1332, 1992).

Human Topoisomerase I and Human Topoisomerase II Alpha available from TopoGEN.

Article Source: Nucleic Acids Research

Topoisomerase II is required for the production of long Pol II gene transcripts in yeast

Abstract
The extent to which the DNA relaxation activities of eukaryotic topoisomerases (topo I and topo II) are redundant during gene transcription is unclear. Although both enzymes can often substitute for each other in vivo, studies in vitro had revealed that the DNA cross-inversion mechanism of topo II relaxes chromatin more efficiently than the DNA strand-rotation mechanism of topo I. Here, we show that the inactivation of topo II in budding yeast produces an abrupt decrease of virtually all polyA+ RNA transcripts of length above ~3 kb, irre- spective of their function. This reduction is not related to transcription initiation but to the stall of RNA polymerase II (Pol II) during elongation. This reduction does not occur in topo I mutants; and it is not avoided by overproducing yeast topo I or bac- terial topo I, which relaxes (-) DNA supercoils. It is rescued by catalytically active topo II or a GyrBA enzyme, which relaxes (+) DNA supercoils. These findings demonstrate that DNA relaxation activities of topo I and topo II are not interchangeable in vivo. Apparently, only topo II relaxes efficiently the (+) DNA supercoils that stall the advancement of Pol II in long genes. A mechanistic model is proposed.

Nucleic Acids Research, 2012, Vol. 40, No. 16 7907–7915 doi:10.1093/nar/gks626

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