P. Forterre, A. Bergerat, D. Gadelle and Cyril Buhler


Abstract of P. Forterre's talk at "The Eighth Conference on DNA Topoisomerases in Therapy" meeting held in Amsterdam,The Netherlands, October 15-17 1997.

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.


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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)