AN ATYPICAL TOPOISOMERASE-II FROM ARCHAEA WITH IMPLICATIONS FOR MEIOTIC RECOMBINATION

Type II topoisomerases help regulate DNA topology during transcription , replication and recombination by catalysing DNA strand transfer thro ugh transient double-stranded breaks(1). All type II topoisomerases de scribed so far are members of a single protein family(2). We have clon ed and sequenced the genes encoding the A and B subunits of topoisomer ase II from the archaeon Sulfolobus shibatae. This enzyme is the first of a new family. It has no similarity with other type II topoisomeras es, except for three motifs in the B subunit probably involved in ATP binding and hydrolysis. We also found these motifs in proteins of the Hsp90(3) and MutL(4) families. The A subunit has similarities with fou r proteins of unknown function. One of them, the Saccharomyces cerevis iae Spo11(5) protein, is required for the initiation of meiotic recomb ination. Mutagenesis, performed on SPO11, of the single tyrosine conse rved between the five homologues shows that this amino acid is essenti al for Spo11 activity. By analogy with the mechanism of action of know n type II topoisomerases, we suggest that Spell catalyses the formatio n of double-strand breaks that initiate meiotic recombination in S. ce rvisiae.