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We are part of the Department of Structural Biology and Chemistry in Institut Pasteur, Paris.
We use experimental techniques such as crystallography and cryo-electron microscopy to visualize at the atomic level the structure of molecules essential to life and to understand their functional properties, especially for
We complement them with computational approaches such as molecular dynamics (atomic models), normal modes dynamics (coarse-grained models) and statistical thermodynamics, in order to go beyond the essentially static pictures given by these methods.
When possible we study their structure in the context of their partners in larger macromolecular complexes and try to dissect the molecular interactions between them
in order to understand possible emerging collective properties (systems biology).
Our main goal is to understand how these molecular machines work at the atomic level so as to design structure-inspired drugs (pharmacology and drug discovery) and re-design their active site(s) to make them accept other substrates (synthetic biology).
Publications on Polymerases by year (2009-2021)
-New article by Dariusz Czernecki et al. in Nucleic Acids Res. Here.
-New article by Clement Madru et al. on a new and very efficient way to express and purify in E. coli the different subunits constituting the RNA polymerase of SARS2-Covid19 in PLoS One Here.
-New article in Biomolecules by C. Samson et al. on the structures of key intermediates in the reaction of a DNA polymerase evolved to accept xeno-nucleotides and its substrates
-New article in Nature Commun. by C. Madru et al. on the cryo-EM structure of archaeal DNA polymerase polD + DNA + PCNA (Here).
-A structural model for the interaction of human Pol mu with an NHEJ junction containing a DNA double-strand-break, published in JBC, see .
This is a collaboration with the group of M.R. Lieber (USA).
-Cryo-EM structure of the polD DNA polymerase (DP1+DP2) complex, with or without DNA, in PLoS Biol.
-An updated structure-based classification of all extant DNA polymerases (Here).
-Talk at the Fifth DNA Polymerases Meeting in Leiden, NL (Program here).
-Design of a polymerase that generates libraries of random RNA polymers in Nucleic Acids Res.
DNA Polymerases and DNA Repair
-X-ray structure of Archaeal polD DNA polymerase reveals a catalytic site similar to multi-subunit RNA polymerases that are found in all domains of life,
by L. Sauguet, P. Raia, G. Henneke and M. Delarue (Nature Commun).
See Recomm by F1000.
-Structural basis for an unexpected "in trans" templated activity by TdT: implications for V(D)J recombination and DNA double-strand-breaks repair in eukaryotes, by
J. Loc'h, S. Rosario and M. Delarue (Structure).
See Recomm by F1000.
-TdT structures by J. Gouge in complex with a DNA synapsis shed new light on DNA Double-Strand-Break Repair by NHEJ (EMBO J., Mar 2015).
-Snapshots of TdT caught in action: dynamical aspects of the two-metal-ion mechanism by J. Gouge et al. (J. Mol. Biol., Jul 2013)
-Structures of inhibitors of TdT, with G. Maga (Milan) and R. di Santo (Roma), J. Med. Chem., Sep 2013.
-Structure of Archaeal DNA polymerase (polB) from P. abyssi in editing mode by J. Gouge et al. (JMB)
-Extensive mutational analysis of TdT and different ways to transform it into a template-directed DNA polymerase by F. Romain et al. in Nucleic Acids Research NAR