Site-specific DNA cleavage by Chlorella virus topoisomerase II

John M. Fortune, Jennifer S. Dickey, Oleg V. Lavrukhin, James L. Van Etten, R. Stephen Lloyd, Neil Osheroff

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The DNA cleavage reaction of topoisomerase II is central to the catalytic activity of the enzyme and is the target for a number of important anticancer drugs. Unfortunately, efforts to characterize this fundamental reaction have been limited by the low levels of DNA breaks normally generated by the enzyme. Recently, however, a type II topoisomerase with an extraordinarily high intrinsic DNA cleavage activity was isolated from Chlorella virus PBCV-1. To further our understanding of this enzyme, the present study characterized the site-specific DNA cleavage reaction of PBCV-1 topoisomerase II. Results indicate that the viral enzyme cleaves DNA at a limited number of sites. The DNA cleavage site utilization of PBCV-1 topoisomerase II is remarkably similar to that of human topoisomerase IIα, but the viral enzyme cleaves these sites to a far greater extent. Finally, PBCV-1 topoisomerase II displays a modest sensitivity to anticancer drugs and DNA damage in a site-specific manner. These findings suggest that PBCV-1 topoisomerase II represents a unique model with which to dissect the DNA cleavage reaction of eukaryotic type II topoisomerases.

Original languageEnglish (US)
Pages (from-to)11761-11769
Number of pages9
JournalBiochemistry
Volume41
Issue number39
DOIs
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Biochemistry

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