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6 Mechanistic Aspects of Type-I Topoisomerases

James J. Champoux


Topoisomerases were first recognized by virtue of their ability to relax closed circular, negatively supercoiled DNA. The prokaryotic and eukaryotic enzymes were originally referred to as the ω protein (Wang 1971) and the DNA untwisting enzyme (Champoux and Dulbecco 1972), respectively. Because the relaxed structure of the closed DNA persists after removal of the protein, it is clear that the enzymes change the topological property called the linking number. In addition to altering the linking number, these enzymes were also shown to catalyze the inter-conversion of other kinds of topological isomers of DNA, and hence, they belong to the general class of enzymes now referred to as DNA topoisomerases. A change in the linking number of a closed circular DNA requires breakage and reclosure of one or both strands of the DNA. Topoisomerases are subdivided into two categories based on the number of strands broken during each cycle of breakage and reclosure. Type-I enzymes, the subject of this chapter (for recent reviews, see Maxwell and Gellert 1986; Sadowski 1986; Wang 1987), alter the linking number by introducing a transient single-strand break in duplex DNA, whereas type-II enzymes act by making transient double-strand breaks. Type-I topoisomerases have been found to change the linking number of the DNA by one (or possibly more), whereas type-II enzymes characteristically change the linking number in steps of two.

Since catalysis by the eubacterial and eukaryotic type-I enzymes proceeds without the need for an energy-donating cofactor, the temporary breaks introduced into the DNA must...

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