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Introduction

We are part of the Department of Structural Biology and Chemistry in Institut Pasteur, Paris.
Our main field is Structural Molecular Biology and Biophysics, augmented by tools of Computational Biology.

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
- RNA and DNA polymerases involved in genome replication or transactions (repair, transcription, transposition...)

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)

2021

-New article by Dariusz Czernecki et al. in Nucleic Acids Res. Here.
on the DNA polymerase of bacteriophage PhiVC8 and its role in helping to replace all adenines by 2-amino-adenines (2-6 diaminopurine) in its genome to avoid the restriction enzymes of its bacterial host.
This is the first time this property is studied at the molecular level since the discovery of the S-2L phage in 1977 by a Russian team Here.
Here is a description of the chemical nature of 2-amino-adenine and its base-pairing with thymine 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.

2020

-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 Ref.
This paper identifies for the first time a 1-nucleotide backtracked complex, on the pathway to the editing complex Text.

-New article in Nature Commun. by C. Madru et al. on the cryo-EM structure of archaeal DNA polymerase polD + DNA + PCNA (Here).

2019

-A structural model for the interaction of human Pol mu with an NHEJ junction containing a DNA double-strand-break, published in JBC, see Access the
recommendation on F1000Prime. 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).

2018

-Review on TdT in Current Opinion in Structural Biology (on line and Recomm by F1000) and PDF.

-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.

2017

2016

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.

2015

-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).
This is the first structure of a polX in a complex with a broken DNA, showing how the two ends are brought together by a mold coming from the protein.

2014

2013

-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.

2012

-Structure of Archaeal DNA polymerase (polB) from P. abyssi in editing mode by J. Gouge et al. (JMB)

2011

2010

2009

-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




  Marc Delarue http://lorentz.dynstr.pasteur.fr