Date : 5/03/2010

Laboratory

Molecular Biology of the gene in Extremophiles CNRS UMR8621
Institut de Génétique et Microbiologie 91405 Orsay
Director : Jean-Pierre Rousset

PhD Supervisor

Patrick Forterre
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phone : +33 33169157489

Subjects / Tools-Methodologies

1 : DNA topoisomerase/Biochemistry
2 : Evolution/Molecular Biology
3 : Enzymology/Single molecule analysis

Summary of lab's interests

Our laboratory is working on mechanisms related to the maintenance of genome integrity in hyperthermophilic archaea. We are especially focusing on mechanisms common to Archaea and Eukarya. We are interested in the origin and evolution of these mechanisms to better undersand the evolutionary relationships between Archaea and Eukaryotes. We are also fascinated by the role that viruses may have played in the origin and evolution of mechanisms related to DNA metabolism. A major line of research in our group has always been the study of DNA topoisomerases. Archaea possess indeed unique DNA topoisomerases such as reverse gyrase, Topo V and Topo VI. The aim of the proposed project is to boost our work on Topo VI that is the prototype of a new type II DNA topoisomerase family.

Summary of project

Our laboratory has isolated a few years ago a new type of DNA topoisomerase II in Archaea, that has been called Topo VI (Bergerat t al., Nature 1997). This enzyme turns out to be the prototype of a new DNA topoisomerase II family, the Topo IIB family. The structure of two archaeal Topo VI have been recently solved, one of them in collaboration with our group (Graille et al., Structure, 2008). Whereas Topo IIA, such as DNA gyrase or eukaryotic Topo II, have been extensively studied for their mechanisms of action and modes of inhibition by antibiotics or antitumoral drugs, few studies have been performed on Topo IIB. The project will thus focus on the mechanism of action and drug sensitivity of several Topo II in collaboration with biophysic laboratories. Studies will be performed on mesophilic Topo IIB to initiate single molecule studies. In addition to an archaeal Topo VI, two new Topo IIB that we have recently identified in genome sequences will be analyzed: a Topo VI from plasmodium and a viral Topo IIB variant than we call Topo VIII. The aim of the project is both to get new insights on the origin and evolution of topoisomerases by comparing Topo IIA and Topo IIB and to identify new drug tagets, especially in the case of Plasmodium.