DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote

Abstract

THE DNA topoisomerases are ubiquitous enzymes that fulfil vital roles in the replication, transcription and recombination of DNA by carrying out DNA-strand passage reactions^1–7. Here we characterize a prokaryotic counterpart to the eukaryotic topoisomerase I in the hyperthermophilic methanogen Methanopyrus handleri^8–10. The new enzyme, called topoisomerase V, has the following properties in common with eukaryotic topoisomerase I, which distinguish it from all other known prokaryotic topoisomerases: (1) its activity is Mg²⁺-independent; (2) it relaxes both negatively and positively supercoiled DNA; (3) it makes a covalent complex with the 3' end of the broken DNA strand; and (4) it is recognized by antibody raised against human topoisomerase I. Eukaryotic-like enzymes have been discovered in some hyperthermophilic prokaryotes, namely the eocytes¹¹ and the extremely thermophilic archaebacteria¹², and hyperthermophilic homologues of eukaryotic DNA polymerase-α, transcription factor IIB and DNA ligase^13–15 have all been reported. Thus our findings support the idea that some essential parts of the eukaryotic transcription–translation and replication machineries were in place before the emergence of eukaryotes, and that the closest living relatives of eukaryotes may be hyperthermophiles.