A New Family of Type II
Topoisomerase (VI) Discovered in Archaea and its Eukaryotic
Homologues
P. Forterre, A. Bergerat, D. Gadelle and Cyril Buhler
Institut de Génétique et Microbiologie,
Université Paris-Sud, CNRS URA 1354, 91405 Orsay
Cedex, France.
The comparison of molecular mechanisms in the three
domains of life : Archaea, Bacteria and Eukaryote, should
help to reconstitute the last universal common ancestor
(LUCA). At the molecular level, Archaea exhibit a mixture of
bacterial and eucaryal features as well as unique ones. In
the case of topoisomerases, Archaea from different lineages
also exhibit different pattern of enzymes and activities. In
particular, hyperthermophilic archaea have a unique pattern
of DNA topology and DNA topoisomerases: their intracellular
plasmids are from relaxed to positively supercoiled and they
contain a unique type I DNA topoisomerases, reverse gyrase,
which induces positive supercoiling in vitro (1-4). We have
now identified a new family of type II DNA topoisomerases
(Topo VI) which are widely distributed in hyperthermophilic
archaea (4). These enzymes are tetrameric (A2B2) with one
subunit (B) bearing a putative ATP-binding site and the
other one (A) probably involved in DNA cleavage. These
subunits exhibit no sequence similarities with classical
topoisomerases II except at the level of their putative ATP
binding site. Comparison of Topo VI and classical
topoisomerases allowed us to define a putative new ATP
module also present in proteins of the MutL and Hsp90
families (4). The A subunit of Topo VI exhibits similarities
with the yeast protein Spo11 which is involved in formation
of double-stranded breaks for initiation of meiotic
recombination (4). We have now expressed the A and B
subunits of the Sulfolobus shibatae TopoVI in E.
coli and shown that the B subunit exhibits an ATPase
activity. We are also looking for a putative Topo VI
activity in yeast. These results show that the study of
Archaea is not only interesting from an evolutionary
perspective, but can have also important implications for
the molecular biology of eucaryotes.
1- Duguet, M. In Nucl. Acids and mol. Biol. 8, 84-114
(1995)
2- Forterre, P., Bergerat, A. and Lopez-Garcia, P. FEMS
Microbiol. Rev. 18, 237-248 (1996)
3 - Lopez-garcia, P and Forterre, P. Mol. Microbiol. 23,
1267-1279 (1997)
4- Bergerat A. De Massy, B., Gadelle, D., Varoutas, P.C.,
Nicolas, A. and Forterre, P.Nature, 386, 414-417 (1997)
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