10 Genetics of DNA Topoisomerases

Abstract

I. INTRODUCTION
This chapter concentrates on DNA topoisomerase genes and mutants from Escherichia coli and from the two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe. It is in these species that the greatest amount of work has been done.

II. E. COLI DNA TOPOISOMERASE MUTANTS
E. coli has three topoisomerases, DNA topoisomerase I, originally called ω protein (Wang 1971), DNA gyrase (Gellert et al. 1976), and DNA topoisomerase III (Dean et al. 1983; Srivenugopal et al. 1984; DiGate and Marians 1988). Topoisomerase I is a monomer of about 97 kD. DNA gyrase (topoisomerase II) is a tetramer of the A₂B₂ type; the molecular masses of the A and B subunits are about 97 kD and 90 kD, respectively. Topoisomerase III is a monomer of 74 kD. Topoisomerase I and gyrase from other eubacteria are similar in size and enzymatic properties to their E. coli counterparts. Topoisomerase III has not yet been identified in other bacterial species.

The E. coli gyrase genes were known even before gyrase was discovered; they were defined by mutations causing resistance to two antibacterial drugs, nalidixic acid and coumermycin. The genes, initially called nalA and cou and now called gyrA and gyrB, code for the A and B subunits of gyrase, respectively. In E. coli, these two genes are far apart, at 48 and 83 minutes, respectively, on the genetic map. In Bacillus subtilis, the genes are adjacent and within a few kilobases of the origin of DNA replication (Moriya et al. 1985). The gyrase genes from...