Structural similarities between topoisomerases that cleave one or both DNA strands

Structural similarities between topoisomerases that cleave one or both DNA strands

^*Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142; and ^§Department of Molecular and Cellular Biology and ^¶Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138

Contributed by Stephen Harrison

Abstract

Type IA and type II DNA topoisomerases are distinguished by their ability to cleave one or two strands, respectively, of a DNA duplex. Both types have been proposed to use an “enzyme-bridging” mechanism, in which a break is formed in a DNA strand and a gap is opened between the broken pieces to allow passage of a second DNA strand or duplex segment. Although the type IA and type II topoisomerase structures appear overall quite different from one another, unexpected similarities between several structural elements suggest that members of the two subfamilies may use comparable mechanisms to bind and cleave DNA.

DNA cleavage/DNA binding/catabolite-activator protein-like domain/Rossmann fold

Footnotes

↵ † Present address: Department of Molecular and Cell Biology, Stanley Hall, University of California, Berkeley, Berkeley, CA 94720.
↵ ‡ Present address: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
↵ ** To whom reprint requests should be addressed. e-mail: schadmin{at}crystal.harvard.edu.
ABBREVIATIONS:

CAP,

catabolite-activator protein;

HTH,

helix–turn–helix