7 Mechanistic Aspects of Type-II DNA Topoisomerases

Abstract

Escherichia coli DNA topoisomerase I and II (Wang and Liu 1979) were names given to the ω protein (Wang 1971) and DNA gyrase (Gellert et al. 1976b), respectively, to distinguish these two enzymes from the same organism. Later developments showed that these two enzymes differ in their mechanisms of action: The former breaks and rejoins one DNA strand at a time, and the latter breaks and rejoins a pair of strands in a duplex DNA in a somewhat concerted manner. This mechanistic difference provides the basis for classifying E. coli DNA topoisomerase I and other activities that break and rejoin one DNA strand at a time as type-I DNA topoisomerases and E. coli gyrase and other activites that transiently break duplex DNAs as type-II DNA topoisomerases (Brown and Cozzarelli 1979; Liu et al. 1980). Several reviews have appeared and covered the various stages of development in the field (Wang and Liu 1979; Cozzarelli 1980; Gellert 1981; Liu 1983; Wang 1985; Maxwell and Gellert 1986). This chapter summarizes the mechanistic aspects of type-II DNA topoisomerases and some of their biochemical properties that bear directly on their mechanism of action.

I. INTERCONVERSION OF DNA TOPOISOMERS
As a consequence of the transient breakage of DNA strands and the passage of duplex DNA segments through these breaks, a type-II DNA topoisomerase can alter the topology of DNA rings (Fig. 1). It is well established that covalently closed circular duplex DNA can serve as a substrate in these reactions, which reflects the double-stranded cleavage and...