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Genome expression and repair

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Genome expression and repair

DEPARTMENT

Functional genomics and cancer

TEAM LEADER

Frederic COIN

Transcription, one of the key steps in gene expression in response to various stimuli in the body, such as stress or hormones, requires a combination of factors. The harmful action of chemical or physical agents that cause damage to DNA disrupts gene expression. If these lesions are not removed by effective repair systems, they will cause mutations that can lead to cancer or increase aging. TFIIH, a complex made up of ten subunits, plays a key role in both gene transcription and gene repair. Mutations in some of the TFIIH subunits are responsible for three genetic diseases, xeroderma pigmentosum (XP), trichotyodystrophy (TTD) and Cockayne syndrome (CS), the phenotype of which results from defects in both DNA repair and gene expression. XP patients develop melanoma very early in life, while TTD and CS patients age prematurely. With the help of biochemistry, genetics and cell biology, we are studying the mechanisms of aging and cancer in various cell systems and animal models deficient in DNA repair and transcription. We are also developing a research axis on melanoma aimed in particular at establishing new therapeutic solutions against this cancer.

Current projects

Our objective is to improve our understanding of the mechanisms that regulate the expression of genes encoding proteins at the transcriptional level and their maintenance of their integrity. The growing amount of data shows that the expression and maintenance of the integrity of genetic information are intimately linked. Errors in each of these crucial cellular mechanisms lead to somatic or hereditary diseases like cancer, but are also involved in natural mechanisms like aging. Our team tries to answer the following questions :

  • How do repair and transcription factors participate in the transactivation of specific genes? • How is transcription related to DNA repair?
  • How do mutations found in genetic diseases affect the transcriptional program of a specific cell that causes somatic diseases such as cancer or hormonal dysfunction?
  • How does the effectiveness of removing DNA damage play a role in cancer treatment or aging?
  • Can we target DNA expression or repair to kill cancer cells?
  • What are the transcriptional deregulations that predominate in cancer cells?

 

 

 

 

Collaborations and networks

  • Dr. Poterszman, IGBMC: Structure/function of TFIIH
  • Dr. Davidson, IGBMC: TFIIH and melanoma
  • Dr. Ali Hamiche, IGBMC: Chromatine remodeling and histone variants 
  • Pr J. Kraemer, National Cancer Institute, Bethesda, USA: XP, CS and TTD patients 
  • Pr. M. Zurita, Universidad Nacional Autónoma de México, Cuernavaca, Mexico: Drosophila models of XP, CS and TTD
  • Dr. J. Svestrup, Clare Hall Laboratories, Cancer Research UK London Research Institute, UK: Gene expression 
  • Dr. P. Brousset, Université Paul-Sabatier, Toulouse, France: Biology of cancer 

Funding and partners

ANR

Fondation ARC

INCA

Labélisation Ligue contre le Cancer

PharmaMar company 

Awards and recognitions

  • Prix scientifique - Comité Alsace de la Fondation pour la Recherche Médicale (FRM) - 2014
  • Prix Olga Sain - La ligue contre le cancer - 2013
  • Grand Prix - Fondation pour la recherche médicale (FRM) - 2012
  • Prix Henry et Mary-Jane Mitjaville - Académie Nationale de Médecine - 2009
  • Prix Duquesne - Ligue Nationale contre le Cancer de Paris - 2009
  • Prix Charles-Louis de Saulses de Freycinet - Institut de France de l'Académie des Sciences - 2008
  • ERC Advanced grant - European Research Council (ERC) - 2008
  • Membre de l'Académie des sciences - Académie des sciences - 2006
  • Chevalier de la Légion d’Honneur - Etat français - 2006
  • Grand Prix - Inserm - 2004
  • Prix AGF/Athena - Institut de France de l'Académie des Sciences - 2002
  • Prix Descartes - European Economic Community - 2000
  • Membre de l'organisation européenne de biologie moléculaire (EMBO) - European Molecular Biology Organization (EMBO) - 1998
  • Prix Européen Jeanne Loubaresse - Institut Curie - 1997
  • Chevalier de l'Ordre National du Mérite - Etat français - 1996
  • Prix Tartois - Fondation pour la Recherche Médicale (FRM) - 1996

Publications