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 through transient double-stranded breaks. All type II topoisomerases described so far are members of a single protein family. We have cloned and sequenced the genes encoding the A and B subunits of topoisomerase II from the archaeon Sulfolobus shibatae. This enzyme is the first of a new family. It has no similarity with other type II topoisomerases, 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 and MutL families. The A subunit has similarities with four proteins of unknown function. One of them, the Saccharomyces cerevisiae Spo11 protein, is required for the initiation of meiotic recombination. Mutagenesis, performed on SPO11, of the single tyrosine conserved between the five homologues shows that this amino acid is essential for Spo11 activity. By analogy with the mechanism of action of known type II topoisomerases, we suggest that Spo11 catalyses the formation of double-strand breaks that initiate meiotic recombination in S. cerevisiae.
Bergerat
A
A
Institut de Génétique et Microbiologie, Université Paris Sud, CNRS URA 1354, Orsay, France.
de Massy
B
B
Gadelle
D
D
Varoutas
P C
PC
Nicolas
A
A
Forterre
P
P
D000595:Amino Acid Sequence; D019843:Archaeal Proteins; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D008540:Meiosis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D016944:Sulfolobus / Q000201:enzymology*
D019843:Archaeal Proteins; D005656:Fungal Proteins; D004247:DNA; C105141:DNA topoisomerase VI; D004250:DNA Topoisomerases, Type II