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 journalArticle

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
Publication statusPublished - Oct 1 2002

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fortune, J. M., Dickey, J. S., Lavrukhin, O. V., Van Etten, J. L., Lloyd, R. S., & Osheroff, N. (2002). Site-specific DNA cleavage by Chlorella virus topoisomerase II. Biochemistry, 41(39), 11761-11769. https://doi.org/10.1021/bi025802g