Site-specific DNA cleavage by Chlorella virus topoisomerase II

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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Chlorella
Type II DNA Topoisomerase
DNA Cleavage
Viruses
DNA
Enzymes
DNA Breaks
Pharmaceutical Preparations
DNA Damage
Catalyst activity

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

Site-specific DNA cleavage by Chlorella virus topoisomerase II. / Fortune, John M.; Dickey, Jennifer S.; Lavrukhin, Oleg V.; Van Etten, James L.; Lloyd, Robert (Stephen); Osheroff, Neil.

In: Biochemistry, Vol. 41, No. 39, 01.10.2002, p. 11761-11769.

Research output: Contribution to journalArticle

Fortune, JM, Dickey, JS, Lavrukhin, OV, Van Etten, JL, Lloyd, RS & Osheroff, N 2002, 'Site-specific DNA cleavage by Chlorella virus topoisomerase II', Biochemistry, vol. 41, no. 39, pp. 11761-11769. https://doi.org/10.1021/bi025802g
Fortune JM, Dickey JS, Lavrukhin OV, Van Etten JL, Lloyd RS, Osheroff N. Site-specific DNA cleavage by Chlorella virus topoisomerase II. Biochemistry. 2002 Oct 1;41(39):11761-11769. https://doi.org/10.1021/bi025802g
Fortune, John M. ; Dickey, Jennifer S. ; Lavrukhin, Oleg V. ; Van Etten, James L. ; Lloyd, Robert (Stephen) ; Osheroff, Neil. / Site-specific DNA cleavage by Chlorella virus topoisomerase II. In: Biochemistry. 2002 ; Vol. 41, No. 39. pp. 11761-11769.
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