Catenation and knotting of duplex DNA by type 1 topoisomerases: a mechanistic parallel with type 2 topoisomerases.

Abstract

Escherichia coli .omega. protein, a type 1 topoisomerase, can catenate and knot duplex DNA circles. Previously, these activities were thought to be limited to type 2 topoisomerases. Catenation by .omega. requires a nick in one of the participating molecules, but it is not necessary that both be nicked. Catenation does not depend on sequence homology and is greatly stimulated by DNA-condensing agents such as spermidine. A eukaryotic type 1 topoisomerase can also interlock duplex DNA circles. These activities cannot easily be explained by the widely held topoisomerase model model in which a reversible nick in DNA allows free rotation about the unbroken strand; instead, passage of a DNA segment through a transient enzyme-bridged break in a single DNA strand is suggested. This is analogous to the sign inversion mechanism of the type 2 topoisomerases, and thus expresses an essential mechanistic unity among topoisomerases. As expected for relaxation by a single-strand passage, .omega. changes the linking number of DNA in steps of 1.