Genome expression and repair
Transcription, one of the key steps of gene expression in response to different stimuli of the organism like stress or hormones, requires a combination of factors. The deleterious action of physical or chemical agents that create lesions in the DNA disrupts the expression of genes. If these lesions are not removed by efficient repair systems they will be at the origin of mutations that can lead to cancer and aging. TFIIH, a multi-subunit complex that plays a pivotal role in both the transcription of genes and their repair. Mutations in some of the subunits of TFIIH are responsible for three genetic diseases (xeroderma pigmentosum (XP), trichotyodystrophy (TTD) and Cockayne syndrome (CS)), the phenotypes of which result from defects in both DNA repair and gene expression. For instance, TTD patients present brittle hairs and nails, that cannot account from a defect in DNA repair and that can be recapitulated in mouse TTD models. With the help of biochemical, genetic and cellular biology we study ageing and cancer predisposition in various cellular systems and animal models deficient in DNA repair and transcription processes.
Our aim is to improve our understanding of the mechanisms that regulate the expression of protein coding genes at the transcriptional level and the maintenance of their integrity. Increasing amount of data indicates that expression and maintenance of the integrity of the genomic information are deeply linked. Defaults in each of these crucial cellular mechanisms are responsible of somatic and inherited diseases like cancers but are also involved in ageing.
We would like to answer the following points:
· How does TFIIH participate in the transactivation of specific genes?
· How is transcription connected with DNA repair?
· How mutations found in XP, CS or TTD affected the transcriptional program of a specific cell to stem for somatic diseases like cancer or hormonal dis-functions?
· How efficiencies of DNA lesions removal play a role in the treatment against cancer?
In a more applied aspect of our work we would like to use IPs cells from XP/TTD or CS patients to correct some of the phenotypes of the patients.
- Dr J. Hoeijmakers, ERASMUS University, Rotterdam, Netherlands
- Pr J. Kraemer, National Cancer Institute, Bethesda, USA
- Pr. M. Zurita, Universidad Nacional Autónoma de México, Cuernavaca, Mexico
- Pr. E. Borrelli, University of California, Irvine, California, USA
- Dr. J. Svestrup, Clare Hall Laboratories, Cancer Research UK London Research Institute, UK
- Dr. P. Brousset, Université Paul-Sabatier, Toulouse, France
- Frédéric COIN - Scientific prize - Comité Alsace de la Fondation pour la Recherche Médicale (FRM) - 2014
- Nicolas LE MAY - Prix Olga Sain - La ligue contre le cancer - 2013
- Jean-Marc EGLY - Grand Prize - Fondation pour la recherche médicale (FRM) - 2012
- Jean-Marc EGLY - Henry et Mary-Jane Mitjaville Prize - Académie Nationale de Médecine - 2009
- Jean-Marc EGLY - Duquesne Prize - Ligue Nationale contre le Cancer de Paris - 2009
- Frédéric COIN - Charles-Louis de Saulses de Freycinet Prize - Institut de France de l'Académie des Sciences - 2008
- Jean-Marc EGLY - ERC Advanced grant - European Research Council (ERC) - 2008
- Jean-Marc EGLY - Member of the French Academy of science - Académie des sciences - 2006
- Jean-Marc EGLY - Chevalier of the Legion of Honour - Etat français - 2006
- Jean-Marc EGLY - Grand Prize - Inserm - 2004
- Jean-Marc EGLY - AGF/Athena Award - Institut de France de l'Académie des Sciences - 2002
- Jean-Marc EGLY - Descartes Prize - European Economic Community - 2000
- Jean-Marc EGLY - Member of the European Molecular Biology Organization (EMBO) - European Molecular Biology Organization (EMBO) - 1998
- Jean-Marc EGLY - Jeanne Loubaresse European Award - Institut Curie - 1997
- Jean-Marc EGLY - Chevalier of the National Order of Merit - Etat français - 1996
- Jean-Marc EGLY - Tartois Award - Fondation pour la Recherche Médicale (FRM) - 1996
- Aug. 25, 2014 - Towards a better understanding of DNA repair and related diseases
- Feb. 6, 2014 - Improving chemotherapy by preventing the repair of tumor cells
- July 4, 2013 - Learn to stop, to better carry on…
- Oct. 25, 2012 - PARG: a new target for therapies against cancer?
- Aug. 26, 2011 - Discovery of a Molecular Signature of Intellectual Disability
- April 9, 2010 - DNA and its complexes
PLoS One Sept. 11, 2015 ; 10:e0138262 .
Mol Carcinog Dec 2015 ; 54:1686-99 .
Mol Cell Aug. 20, 2015 ; 59:513-4 .
Cell Mol Life Sci Jun 2015 ; 72:2177-86 .
J Biol Chem March 27, 2015 ; 290:8321-30 .
Am J Hum Genet Feb. 5, 2015 ; 96:194-207 .
Proc Natl Acad Sci U S A Feb. 3, 2015 ; 112:1499-504 .
PLoS One Sept. 30, 2014 ; 9:e108957 .
PLoS Biol Sept. 30, 2014 ; 12:e1001954 .
PLoS Genet Oct. 23, 2014 ; 10:e1004732 .